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Xinfuli Granule improves post-myocardial infarction ventricular remodelingand myocardial fibrosis in rats by regulating TGF-β/Smads signaling pathway 被引量:19
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作者 Jie MA Zhi-Yuan LI +3 位作者 Xiao-Peng LIANG Cai-Xia GUO Pei-Pei LU Li-Hong MA 《Journal of Geriatric Cardiology》 SCIE CAS CSCD 2017年第5期301-307,共7页
Background Recent clinical and experimental studies have confirmed the effects of Xinfuli Granule (XG), a compound Chinesemedicine in the prevention and treatment of heart failure (HF). This study aimed to investi... Background Recent clinical and experimental studies have confirmed the effects of Xinfuli Granule (XG), a compound Chinesemedicine in the prevention and treatment of heart failure (HF). This study aimed to investigate the effects and the mechanisms of XG onventricular reconstruction in rats with acute myocardial infarction (AMI). Methods Sprague-Dawley rats were subjected to left anteriordescending branch ligation. The rats that survived 24 h were randomly assigned to five groups: medium-dose of XG group (MI+XGM),high-dose of XG group (MI+XGH), carvedilol group (MI+C), medium-dose of XG + carvedilol group (MI+C+XGM). Fourteen rats under-went identical surgical procedures without artery ligation, serving as sham controls. At 28 days, left ventricular weight to body weight(LVW/BW) and heart weight to body weight (HW/BW) were calculated; left ventricular ejection fraction (LVEF), left ventricular shorteningfraction (LVFS), left ventricular internal diameter at systole (LVIDS) were measured by ultrasound; HE staining, Masson staining, and Siriusred staining were used to assess the myocardial pathological and physiological changes as well as myocardial fibrosis area and non-infarctzone Ⅰ/Ⅲ collagen ratio. Expression of Smad3 were detected and analyzed by Western blot, immunohistochemistry and immunofluorescenceP-Smad3, Smad2 and Smad7 in the TGF-13/Smads signaling pathway were also analyzed by Western blot. Results The LVIDS (P 〈 0.01),HW/BW (P 〈 0.05), type UIII collagen ratio (P 〈 0.01) and myocardial collagen (P 〈 0.01) decreased significantly while the LVW/BW,LVFS (P 〈 0.05) increased significantly in MI+XGM group as compared with those in other groups. The expression of key signal moleculesof the TGF-β/Smads signaling pathway, including Smad3, P-Smad3 and Smad2 protein were decreased, while the expression of Smad7 in-creased in both XG and carvedilol treatment groups as compared to those of the MI group (all P 〈 0.01). Immunohistochemistry and im-munofluorescence further confirmed the down-regulated Smad3 expression. Conclusion XG can improve ventricular reconstruction andinhibit myocardial fibrosis in rats with AMI by regulating TGF-β/Smads signaling pathway. 展开更多
关键词 Acute MYOCARDIAL INFARCTION MYOCARDIAL fibrosis tgf-β/smads signaling pathway Ventricular remodeling Wnt/β-cateninsignaling pathway Xinfuli GRANULE
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Electroacupuncture improves myocardial fibrosis in heart failure rats by attenuating ECM collagen deposition through modulation of TGF-β1/Smads signaling pathway
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作者 Wen-Hui Wang Qian-Lan Zeng +3 位作者 Jiao-Jiao Zhang Hao-Sheng Wu Sheng-Bing Wu Mei-Qi Zhou 《Traditional Medicine Research》 2024年第8期1-10,共10页
Background: To explore the effects of electroacupuncture on cardiac function and myocardial fibrosis in rat models of heart failure, and to elucidate the underlying mechanism of electroacupuncture in heart failure tre... Background: To explore the effects of electroacupuncture on cardiac function and myocardial fibrosis in rat models of heart failure, and to elucidate the underlying mechanism of electroacupuncture in heart failure treatment. Methods: Healthy male Sprague-Dawley rats were allocated into three groups: Sham group, Model group, and electroacupuncture (Model + EA) group, with each group comprising 8 rats. The model underwent a procedure involving the ligation of the left anterior descending coronary artery to induce a model of heart failure. The Model + EA group was used for 7 consecutive days for electroacupuncture of bilateral Shenmen (HT7) and Tongli (HT5), once a day for 30 min each time. Left ventricular parameters in rats were assessed using a small-animal ultrasound machine to analyze changes in left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular ejection fraction, and left ventricular fractional shortening. Serum interleukin-1β (IL-1β), cardiac troponin (cTn), and N-terminal brain natriuretic peptide precursor levels were measured using ELISA. Histopathological changes in rat myocardium were observed through HE staining, while collagen deposition in rat myocardial tissue was assessed using the Masson staining method. Picro sirius red staining, immunohistochemical staining, and RT-qPCR were utilized to distinguish between the various types of collagen deposition. The expression level of TGF-β1 and SMAD2/3/4/7 mRNA in rat myocardial tissues was determined using RT-qPCR. Additionally, western blot analysis was conducted to assess the protein expression levels of TGF-β1, SMAD3/7, and p-SMAD3 in rat myocardial tissues. Results: Compared with the Sham group, the left ventricular ejection fraction and left ventricular fractional shortening values of the Model group were significantly decreased (P < 0.01);the left ventricular end-diastolic volume and left ventricular end-systolic volume values were remarkably increased (P < 0.01);serum N-terminal brain natriuretic peptide precursor content was increased (P < 0.01);serum IL-1β and cTn levels were increased (P < 0.01);myocardial collagen volume fraction were increased (P < 0.01);and those of the expression of TGF-β1 and SMAD2/3/4 mRNA was increased (P < 0.01);the expression of SMAD7 mRNA was decreased (P < 0.01);the protein expression levels of TGF-β1, SMAD3, and p-Smad3 were increased (P < 0.01);the protein expression level of SMAD7 was decreased (P < 0.01) in the Model group. Compared to the Model group, the expression levels of the proteins TGF-β1, SMAD3, and p-Smad3 in myocardial tissue were found to be decreased (P < 0.01), and the expression level of the protein SMAD7 was found to be increased (P < 0.01) in the Model + EA group;the collagen volume fraction and deposition of type Ⅰ /Ⅲ collagen were decreased (P < 0.01) in the Model + EA group. Conclusion: Electroacupuncture alleviates myocardial fibrosis in rats with heart failure, and this effect is likely due to attributed to the modulation of the TGF-β1/Smads signaling pathway, which helps reduce collagen deposition in the extracellular matrix. 展开更多
关键词 heart failure ELECTROACUPUNCTURE heart meridian of Hand-Shaoyin collagen deposition tgf-β1/smads signaling pathway myocardial fibrosis
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Cinobufotalin prevents bone loss induced by ovariectomy in mice through the BMPs/SMAD and Wnt/β-catenin signaling pathways
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作者 Da-zhuang Lu Li-jun Zeng +8 位作者 Yang Li Ran-li Gu Meng-long Hu Ping Zhang Peng Yu Xiao Zhang Zheng-wei Xie Hao Liu Yong-sheng Zhou 《Animal Models and Experimental Medicine》 CAS CSCD 2024年第3期208-221,共14页
Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy pre... Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy prediction system(DLEPS)is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes.This study aimed to explore the protective effect and potential mechanisms of cinobufotalin(CB),a traditional Chinese medicine(TCM),on bone loss.Methods:DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary osteoporosis.Micro-CT,histological and morphological analysis were applied for the bone protective detection of CB,and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells(hBMMSCs)were also investigated.The underlying mechanism was verified using qRT-PCR,Western blot(WB),immunofluorescence(IF),etc.Results:A safe concentration(0.25mg/kg in vivo,0.05μM in vitro)of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of hBMMSCs.Both BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation,further regulating the expression of osteogenesis-associated factors,and ultimately promoting osteogenesis.Conclusion:Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss,further promoting osteogenic differentiation/function of hBMMSCs,with BMPs/SMAD and Wnt/β-catenin signaling pathways involved. 展开更多
关键词 BMPs/smad bone loss cinobufotalin hBMMSCs OSTEOGENESIS OSTEOPOROSIS Wnt/β-catenin signaling pathways
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Berberine Attenuates Cigarette Smoke Extract-induced Airway Inflammation in Mice:Involvement of TGF-β1/Smads Signaling Pathway 被引量:6
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作者 Wen WANG Gan ZHA +3 位作者 Jin-jing ZOU Xun WANG Chun-nian LI Xiao-jun WU 《Current Medical Science》 SCIE CAS 2019年第5期748-753,共6页
Although several studies confirmed that berberine may attenuate airway inflammation in mice with chronic obstructive pulmonary disease(COPD),its underlying mechanisms were not clear until now.We aimed to establish an ... Although several studies confirmed that berberine may attenuate airway inflammation in mice with chronic obstructive pulmonary disease(COPD),its underlying mechanisms were not clear until now.We aimed to establish an experiment mouse model for COPD and to investigate the effects of berberine on airway inflammation and its possible mechanism in COPD model mice induced by cigarette smoke extract(CSE).Twenty SPF C57BL/6 mice were randomly divided into PBS control group,COPD model group,low-dose berberine group and high-dose berberine group,5 mice in each group.The neutrophils and macrophages were examined by Wright's staining.The levels of inflammatory cytokines TNF-α and IL-6 in bronchoalveolar lavage fluid(BALF)were detennined by enzyme-linked immunosorbent assay.The expression levels of TGF-β1,Smad2 and Smad3 mRNA and proteins in lung tissues were respectively detected by quantitative real-time polymerase chain reaction and Western blotting.It was found that CSE increased the number of inflammation cells in BALF,elevated lung inflammation scores,and enhanced the TGF-β1/Smads signaling activity in mice.High-dose berberine restrained the alterations in the COPD mice induced by CSE.It was concluded that high-dose berberine ameliorated CSE-induced airway inflammation in COPD mice.TGF-β1/Smads signaling pathway might be involved in the mechanism.These findings suggested a therapeutic potential of high-dose berberine on the CSE-induced airway inflammation. 展开更多
关键词 BERBERINE CIGARETTE SMOKE extract chronic OBSTRUCTIVE pulmonary disease tgf-β1/smads signaling pathway
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Calcitriol attenuates liver fibrosis through hepatitis C virus nonstructural protein 3-transactivated protein 1-mediated TGF β1/Smad3 and NF-κB signaling pathways 被引量:1
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作者 Liu Shi Li Zhou +13 位作者 Ming Han Yu Zhang Yang Zhang Xiao-Xue Yuan Hong-Ping Lu Yun Wang Xue-Liang Yang Chen Liu Jun Wang Pu Liang Shun-Ai Liu Xiao-Jing Liu Jun Cheng Shu-Mei Lin 《World Journal of Gastroenterology》 SCIE CAS 2023年第18期2798-2817,共20页
BACKGROUND Hepatic fibrosis is a serious condition,and the development of hepatic fibrosis can lead to a series of complications.However,the pathogenesis of hepatic fibrosis remains unclear,and effective therapy optio... BACKGROUND Hepatic fibrosis is a serious condition,and the development of hepatic fibrosis can lead to a series of complications.However,the pathogenesis of hepatic fibrosis remains unclear,and effective therapy options are still lacking.Our group identified hepatitis C virus nonstructural protein 3-transactivated protein 1(NS3TP1) by suppressive subtractive hybridization and bioinformatics analysis,but its role in diseases including hepatic fibrosis remains undefined.Therefore,additional studies on the function of NS3TP1 in hepatic fibrosis are urgently needed to provide new targets for treatment.AIM To elucidate the mechanism of NS3TP1 in hepatic fibrosis and the regulatory effects of calcitriol on NS3TP1.METHODS Twenty-four male C57BL/6 mice were randomized and separated into three groups,comprising the normal,fibrosis,and calcitriol treatment groups,and liver fibrosis was modeled by carbon tetrachloride(CCl4).To evaluate the level of hepatic fibrosis in every group,serological and pathological examinations of the liver were conducted.TGF-β1 was administered to boost the in vitro cultivation of LX-2 cells.NS3TP1,α-smooth muscle actin(α-SMA),collagen I,and collagen Ⅲ in every group were examined using a Western blot and real-time quantitative polymerase chain reaction.The activity of the transforming growth factor beta 1(TGFβ1)/Smad3 and NF-κB signaling pathways in each group of cells transfected with pcDNA-NS3TP1 or siRNA-NS3TP1 was detected.The statistical analysis of the data was performed using the Student’s t test.RESULTS NS3TP1 promoted the activation,proliferation,and differentiation of hepatic stellate cells(HSCs)and enhanced hepatic fibrosis via the TGFβ1/Smad3 and NF-κB signaling pathways,as evidenced by the presence of α-SMA,collagen I,collagen Ⅲ,p-smad3,and p-p65 in LX-2 cells,which were upregulated after NS3TP1 overexpression and downregulated after NS3TP1 interference.The proliferation of HSCs was lowered after NS3TP1 interference and elevated after NS3TP1 overexpression,as shown by the luciferase assay.NS3TP1 inhibited the apoptosis of HSCs.Moreover,both Smad3 and p65 could bind to NS3TP1,and p65 increased the promoter activity of NS3TP1,while NS3TP1 increased the promoter activity of TGFβ1 receptor I,as indicated by coimmunoprecipitation and luciferase assay results.Both in vivo and in vitro,treatment with calcitriol dramatically reduced the expression of NS3TP1.Calcitriol therapy-controlled HSCs activation,proliferation,and differentiation and substantially suppressed CCl4-induced hepatic fibrosis in mice.Furthermore,calcitriol modulated the activities of the above signaling pathways via downregulation of NS3TP1.CONCLUSION Our results suggest that calcitriol may be employed as an adjuvant therapy for hepatic fibrosis and that NS3TP1 is a unique,prospective therapeutic target in hepatic fibrosis. 展开更多
关键词 Nonstructural protein 3-transactivated protein 1 CALCITRIOL Liver fibrosis Hepatic stellate cells Mouse model TGFβ1/smad3 NF-κB signaling pathway
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Effects of Cigu Xiaozhi Formula on miR-378a-3p Expression and Hh Signaling Pathway in TGF-β1 Induced LX2 Cells
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作者 Aidi WANG Yanhua MA +1 位作者 Li WANG Xiuping ZHAO 《Medicinal Plant》 CAS 2023年第5期52-56,71,共6页
[Objectives]To observe the effects of Cigu Xiaozhi Formula on miR-378a-3p expression and Hh signaling pathway in TGF-β1 induced and activated LX2 cells.[Methods]Cells were divided into control group,induction group,d... [Objectives]To observe the effects of Cigu Xiaozhi Formula on miR-378a-3p expression and Hh signaling pathway in TGF-β1 induced and activated LX2 cells.[Methods]Cells were divided into control group,induction group,drug-containing serum group,miR-378a-3p inhibitor group,and miR inhibitor NC group.CCK-8 method was used to detect the cell viability of each group,and flow cytometry was used to detect the apoptosis rate of each group.RT-qPCR was used to detect the expression of miR-378a-3p in each group s cells,and RT-qPCR and Western blot were used to detect mRNA and protein expression of Shh,Gli1,Gli2,Col-I,andα-SMA in each group s cells.[Results]Compared with the control group,the cell viability and expression of Shh,Gli1,Gli2,Col-I,andα-SMA mRNA and protein in induction group increased(P<0.01),while the expression of miR-378a-3p decreased(P<0.01).Compared with the induction group,the cell viability and expression of Shh,Gli1,Gli2,Col-I,α-SMA mRNA andα-SMA and Gli2 protein decreased in drug-containing serum group(P<0.05),while cell apoptosis rate and miR-378a-3p expression increased(P<0.01).In miR-378a-3p inhibitor group,cell viability and the expression of Shh,Gli1,Gli2,Col-I,α-SMA mRNA and Gli1,Gli2,α-SMA protein increased(P<0.05,P<0.01),while the apoptosis rate and miR-378a-3p expression decreased(P<0.05,P<0.01).[Conclusions]Cigu Xiaozhi Formula containing serum can upregulate miR-378a-3p expression and downregulate the expression of Gli2 andα-SMA in TGF-β1 induced LX2 cells,thereby inhibiting the activation of LX2 cells and exerting the effects of anti liver fibrosis. 展开更多
关键词 Cigu Xiaozhi Formula LX2 cells tgf-β1 miR-378a-3p Hh signaling pathway
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Cetirizine regulates scleroderma skin fibrosis in mice via the TGF-β1/Smad3 signaling pathway
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作者 Feng Jian Jing Qi +3 位作者 Xiao-Ying Yang Li-Na Yang Qi Zhang Xiang Li 《Journal of Hainan Medical University》 2020年第14期16-21,共6页
Objective:To investigate the effect of cetirizine on the fibrosis of skin tissue in systemic sclerosis(SSc)mice and its mechanism of action.Methods:Thirty-two BALB/C mice were randomly divided into a blank group,a mod... Objective:To investigate the effect of cetirizine on the fibrosis of skin tissue in systemic sclerosis(SSc)mice and its mechanism of action.Methods:Thirty-two BALB/C mice were randomly divided into a blank group,a model group,a cetirizine low-dose group,and a cetirizine high-dose group,with eight in each group.The blank group was injected with normal saline on the back,and the other three groups were injected with bleomycin on the back to prepare SSc mouse models.The mice were injected once a day for 28 consecutive days,while the normal group and the model group were given saline.The dose group was administrated intragastrically at 2 mg/kg and 5 mg/kg,respectively,for 28 consecutive days.Detect the thickness of the dermis by taking the skin tissue in the back injection area of each group.Hematoxylin-eosin staining(HE)and Masson staining.Sample hydrolysis method to detect hydroxyproline(HYP)content in skin tissue.Immunohistochemical detection ofα-smooth muscle actin(α-SMA)expression in skin tissues.Enzyme-linked immunosorbent assay(ELISA)to detect serum interleukin(IL-6,IL-10)and transforming growth factor(TGF-αand TGF-β1).Quantitative real-time PCR(qRT-PCR)was used to detect the expression levels of collagen type I(COL1A1),type III collagen(COL3A1),Smad homolog 3(Smad3),and TGF-β1 mRNA.Western blot was used to detect the expression levels of COL1A1,COL3A1 and p-Smad3.Results:Compared with the blank group,the dermis thickness and HYP content of the model group increased,the skin tissue lesions and fibrosis were more severe,theα-SMA positive expression intensity in the skin tissue was higher,and the serum IL-6,IL-10,TGF-α,TGF-β1 content increased,COL1A1,COL3A1,Smad3,TGF-β1 mRNA expression levels increased in skin tissues,COL1A1,COL3A1,p-Smad3 protein expression increased,the differences were statistically significant(P<0.05).Compared with the model group,the dermal thickness and HYP content of the low and high dose cetirizine groups were reduced,the degree of skin tissue lesions and fibrosis was improved,the expression ofα-SMA in skin tissues was weakened,the levels of IL-6,IL-10,TGF-α,TGF-β1 in serum were reduced,the expression levels of COL1A1,COL3A1,Smad3 and TGF-β1 in skin tissues were reduced,and the expression levels of COL1A1,COL3A1,and p-Smad3 proteins were reduced,the decrease in the high-dose group was more significant,and the differences were statistically significant(P<0.05).Conclusion:Cetirizine can improve the degree of fibrosis of skin tissue in SSc mice and reduce the immune inflammation response.The mechanism of action is related to the TGF-β1/Smad3 signaling pathway. 展开更多
关键词 SCLERODERMA CETIRIZINE Skin fibrosis tgf-β1/smad3 signaling pathway
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MiR-146a-5p targeting SMAD4 and TRAF6 inhibits adipogenensis through TGF-β and AKT/mTORC1 signal pathways in porcine intramuscular preadipocytes 被引量:10
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作者 Que Zhang Rui Cai +2 位作者 Guorong Tang Wanrong Zhang Weijun Pang 《Journal of Animal Science and Biotechnology》 SCIE CAS CSCD 2021年第1期220-235,共16页
Background: Intramuscular fat(IMF) content is a vital parameter for assessing pork quality. Increasing evidence has shown that microRNAs(miRNAs) play an important role in regulating porcine IMF deposition. Here, a nov... Background: Intramuscular fat(IMF) content is a vital parameter for assessing pork quality. Increasing evidence has shown that microRNAs(miRNAs) play an important role in regulating porcine IMF deposition. Here, a novel miRNA implicated in porcine IMF adipogenesis was found, and its effect and regulatory mechanism were further explored with respect to intramuscular preadipocyte proliferation and differentiation.Results: By porcine adipose tissue miRNA sequencing analysis, we found that miR-146a-5p is a potential regulator of porcine IMF adipogenesis. Further studies showed that miR-146a-5p mimics inhibited porcine intramuscular preadipocyte proliferation and differentiation, while the miR-146a-5p inhibitor promoted cell proliferation and adipogenic differentiation. Mechanistically, miR-146a-5p suppressed cell proliferation by directly targeting SMAD family member 4(SMAD4) to attenuate TGF-β signaling. Moreover, miR-146a-5p inhibited the differentiation of intramuscular preadipocytes by targeting TNF receptor-associated factor 6(TRAF6) to weaken the AKT/mTORC1 signaling downstream of the TRAF6 pathway.Conclusions: MiR-146a-5p targets SMAD4 and TRAF6 to inhibit porcine intramuscular adipogenesis by attenuating TGF-β and AKT/mTORC1 signaling, respectively. These findings provide a novel miRNA biomarker for regulating intramuscular adipogenesis to promote pork quality. 展开更多
关键词 Adipogenesis AKT/mTORC1 signal pathway MiR-146a-5p Porcine intramuscular fat smad4 tgf-βsignal pathway TRAF6
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Lignans from Seeds of Herpetospermum caudigerum Wall.Protect Against Alcoholic Liver Injury via TGF-β/Smads Pathway in Rats 被引量:1
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作者 Qi MA Jian GU +3 位作者 Puyang GONG Maojia LI Ni MA Yanxi LI 《Medicinal Plant》 CAS 2020年第2期54-57,共4页
[Objectives]This study aimed to investigate the effects of lignans from seeds of Herpetospermum caudigerum Wall.(SHC)on expression of TGF-β/Smads in liver tissue of hepatic alcohol-injuried rats,and to explore its pr... [Objectives]This study aimed to investigate the effects of lignans from seeds of Herpetospermum caudigerum Wall.(SHC)on expression of TGF-β/Smads in liver tissue of hepatic alcohol-injuried rats,and to explore its protective mechanism.[Methods]A total of 60 SD rats were randomly divided into six groups.The rats in all the groups except those in the normal group were given with white spirit by gavage for 8 weeks to establish alcoholic liver injury models.After rat models were established successfully,they were administered intragastrically with 400,200 and 100 mg/kg of lignans,respectively.The rats in the normal group were administered intragastrically with 50 mg/kg of silymarin.The administration lasted for 8 weeks,once a day.The changes in the general state,liver tissue pathology and collagen deposition of the rats were observed.The expression of TGF-β,TGF-β1 receptor 1(TβR-I),TGF-β1 receptor 2(TβR-II),Smad2/p-Smad2 and Smad3/p-Smad3 in the hepatic tissue was detected.[Results]The expression levels of TGF-β1,Smad2,p-Smad2,and p-Smad3 significantly declined,and the expression levels of TβR-I,TβR-II and Smad3 did not change significantly in the liver tissue of rats in the lignans groups and the expression levels of TGF-β,Smad2,and p-Smad3 significantly declined.Meanwhile,the expression levels of TβR-I,TβR-II,p-Smad2 and Smad3 did not change significantly in the silymarin group.[Conclusions]The lignans from SHC have significant intervention effects on alcoholic livery injury.The mechanism may be related to the inhibition of hepatic stellate cell(HSC)activation,TGF-βsecretion and p-Smad2,p-Smad3 expression in the signaling pathway. 展开更多
关键词 SHC Lignan ALCOHOLIC liver injury tgf-β/smads pathway
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Role of TGF-βl Signaling in Heart Valve Calcification Induced by Abnormal Mechanical Stimulation in a Tissue Engineering Model 被引量:3
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作者 Xing-jian HU Wen-cong-hui WU +5 位作者 Nian-guo DONG Jia-wei SHI Jun-wei LIU Si CHEN Chen DENG Feng SHI 《Current Medical Science》 SCIE CAS 2018年第5期765-775,共11页
A tissue engineering model of heart valve calcification induced in a bio-reactor was established to evaluate the calcification induced by abnormal mechanical stimulation and explore the underlying molecular mechanisms... A tissue engineering model of heart valve calcification induced in a bio-reactor was established to evaluate the calcification induced by abnormal mechanical stimulation and explore the underlying molecular mechanisms.Polyethylene glycol (PEG)-modified decellularized porcine aortic leaflets seeded with human valve interstitial cells (huVICs)were mounted on a Ti-Ni alloy frame to fabricate two-leaflet and three-leaflet tissue engineered valves.The two-leaflet model valves were exposed to abnormal pulsatile flow stimulation with null (group A),low (1000mL/min,group B),medium (2000mL/min,group C),and high velocity (3000mL/min,group D)for 14 days. Morphology and calcification were assessed by yon Kossa staining,alkaline phosphatase (ALP)content,and Runx2 immunostaining.Leaflet calcification and mRNA and protein expression of transforming growth factor (TGF)-β1,bone morphogenetic protein 2 (BMP2),Smadl,and MSX2 were measured at different time points.ALP content was examined in two-leaflet valves seeded with BMP2 shRNA plasmid-infected huVICs and exposed to the same stimulation conditions.The results showed that during 14 days of flow stimulation,huVICs on the leaflet surface proliferated to generate normal monolayer coverage in groups A,B,and C.Under mechanical stimulation,huVICs showed a parallel growth pattern in the direction of the fluid flow,but huVICs exhibited disordered growth in the high-velocity flow environment,yon Kossa staining,ALP measurement,and immunohistochemical staining for Runx2 confirmed the lack of obvious calcification in group A and significant calcification in group D.Expression levels of TGF-β1,BMP2, and MSX2 mRNA and protein were increased under fluid stimulation.ALP production by BMP2 shRNA plasmid-infected huVICs on model leaflets was significantly reduced.In conclusion,abnormal mechanical stimulation in a bioreactor induced calcification in the tissue engineering valve model.The extent of calcification correlated positively with the flow velocity,as did the mRNA and protein levels of TGF-β1,BMP2,and MSX2.These findings indicate that TGF-β1/BMP2 signaling is involved in valve calcification induced bv abnormal mechanical stimulation. 展开更多
关键词 VALVE CALCIFICATION ABNORMAL mechanical STIMULATION BIOREACTOR tgf-β1 signal pathway
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Research status of E3 ubiquitin ligase Smurf2 and related signaling pathways in glioma
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作者 Qianxu Jin Zongmao Zhao 《Journal of Translational Neuroscience》 2020年第2期1-8,共8页
Glioma is the tumor with the highest incidence in the brain,and it is eager to seek new and efiective treatment.The interaction of ubiquitination and deubiquitination regulates many cell activities in organisms,and pa... Glioma is the tumor with the highest incidence in the brain,and it is eager to seek new and efiective treatment.The interaction of ubiquitination and deubiquitination regulates many cell activities in organisms,and participates in tumor occurrence,development,migration,invasion and other processes.This article summarized the progress of E3 ubiquitination ligase smad ubiquitination regulatory factor 2(Smurf2)and glioma-related signaling pathways to assist clinical diagnosis and treatment of glioma. 展开更多
关键词 GLIOMA smad ubiquitination regulatory factor 2(Smurf2) ubiquitin ligase signaling pathway
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The Effects of Singal Protein SMADs on Rat Cardiocyte Hypertrophy
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作者 黄俊 王梦洪 +3 位作者 肖静 彭景添 郑泽琪 彭小平 《South China Journal of Cardiology》 CAS 2005年第2期77-81,共5页
Objectives To investigate the role of signal protein SMADs in rat cardiac hypertrophy. Methods The rat models of cardiac hypertrophy were produced by constriction of the abdominal aorta. The left vertricular mass ind... Objectives To investigate the role of signal protein SMADs in rat cardiac hypertrophy. Methods The rat models of cardiac hypertrophy were produced by constriction of the abdominal aorta. The left vertricular mass index (LVMI) was investigated. The expression of transforming growth factor-β1 mRNA (TGF-β1) and Smad 2,3,7 mRNA were assessed by RT-PCR. Reslutes The LVMI and the expression of TGF-β1 and Smad 2,3,7mRNA in hypertrophic left ventricule were increased on day 3 after the operation and continued to 4th weeks. The peak expression of TGF-β1 and Smad 2,3 mRNA were in 2 weeks after operation. The expression of Smad 7 was increased in 3 day after operation, but the peak was in 1 week after operation, then decreased. Conclusions The TGF-β1 and signal protein Smad 2,3,7 were included in the progress of rat cardiac hypertrophy produced by constriction of abdominal aorta. 展开更多
关键词 Myocardial hypertrophy tgf-β1 signal protein smads
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Linggui Zhugan Decoction(苓桂术甘汤)Inhibits Ventricular Remodeling after Acute Myocardial Infarction in Mice by Suppressing TGF-β1 Smad Signaling Pathway 被引量:18
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作者 WANG Liang SHI Hui +2 位作者 HUANG Jin-ling XU Shan LIU Pei-pei 《Chinese Journal of Integrative Medicine》 SCIE CAS CSCD 2020年第5期345-352,共8页
Objective:To investigate the inhibitory effect of Linggui Zhugan Decoction(LZD,苓桂术甘汤)on the ventricular remodeling(VR)after acute myocardial infarction(AMI)and related mRNA and proteins expression in transforming... Objective:To investigate the inhibitory effect of Linggui Zhugan Decoction(LZD,苓桂术甘汤)on the ventricular remodeling(VR)after acute myocardial infarction(AMI)and related mRNA and proteins expression in transforming growth factor-beta 1(TGF-β1)/Smad signaling pathway,and explain its putative mechanism.Methods:A VR model was generated by ligation of coronary artery in mice.Two weeks after surgery,60 mice were randomly divided into the model group,the sham-operation group(distilled water),the positive control group(2.4 mg/kg simvastatin),and the low-,medium-and high-dose LZD groups(2.1,4.2,8.4 g crude drug/kg,respectively)by a random number table,10 mice in each group.Mice in each group was treated for 4 weeks.Changes of hemodynamics indices and cardiac weight index were detected by the PowerLab data acquisition and analysis recording instrument.Morphology changes of myocardial tissue were observed by hematoxylin-eosin and Masson staining.The expressions of TGF-β1,Smad2,Smad3,p-Smad2 and p-Smad3 in myocardial tissue were detected by Western blotting.The mRNA expressions of TGF-β1,Smad2 and Smad3 were detected by reverse transcription-quantitative polymerase chain reaction(RT-qPCR).The expressions of matrix metalloprotein 2(MMP2),MMP9,collagenⅠand collagen Ⅲ were observed by immunohistochemical methods.Results:VR mice showed significant dysfunction in hemodynamic indices and cardiac structure and function.Compared with the shamoperation group,myocardial tissue damage,interstitial fibrosis occurred in the model mice,left ventricular systolic pressure(LVSP),left ventricular pressure maximum contraction rate(+dp/dtmax)and left ventricular pressure maximum relaxation rate(-dp/dtmax)decreased significantly(all P<0.01),while left ventricular end-diastolic pressure(LVEDP),cardiac weight index and left ventricular weight index elevated significantly,meanwhile TGF-β1,p-Smad2,p-Smad3,Smad2,Smad3,MMP2,MMP9,collagen Ⅰ,collagen Ⅲ protein expressions in myocardial tissue and TGF-β1 Smad2 and Smad3 mRNA expressions increased significantly(all P<0.01).Compared with the model group,LZD could significantly improve the pathological changes of myocardial tissue,increase LVSP,+dp/dtmax and-dp/dtmaxf lower LVEDP,reduce the whole heart weight index and left ventricular weight index and inhibit the over-expressions of TGF-β1f p-Smad2,p-Smad3,Smad2,Smad3,MMP2,MMP9,collagenⅠand collagenⅢproteins in myocardial tissue and mRNA expressions of TGF-β1 Smad2 and Smad3(P<0.05 or P<0.01).Conclusion:LZD can significantly suppress VR induced by AMI,and its underlying mechanism may be associated with its inhibitory effect on the TGF-β1/Smad signaling pathway. 展开更多
关键词 Linggui Zhugan DECOCTION acute myocardial INFARCTION VENTRICULAR REMODELING transtorming growth FACTOR-BETA 1/smad signaling pathway Chinese medicine
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Cytokine receptor-like factor 1(CRLF1)promotes cardiac fibrosis via ERK1/2 signaling pathway
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作者 Shenjian LUO Zhi YANG +6 位作者 Ruxin CHEN Danming YOU Fei TENG Youwen YUAN Wenhui LIU Jin LI Huijie ZHANG 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2023年第8期682-697,共16页
Cardiac fibrosis is a cause of morbidity and mortality in people with heart disease.Anti-fibrosis treatment is a significant therapy for heart disease,but there is still no thorough understanding of fibrotic mechanism... Cardiac fibrosis is a cause of morbidity and mortality in people with heart disease.Anti-fibrosis treatment is a significant therapy for heart disease,but there is still no thorough understanding of fibrotic mechanisms.This study was carried out to ascertain the functions of cytokine receptor-like factor 1(CRLF1)in cardiac fibrosis and clarify its regulatory mechanisms.We found that CRLF1 was expressed predominantly in cardiac fibroblasts.Its expression was up-regulated not only in a mouse heart fibrotic model induced by myocardial infarction,but also in mouse and human cardiac fibroblasts provoked by transforming growth factor-β1(TGF-β1).Gain-and loss-of-function experiments of CRLF1 were carried out in neonatal mice cardiac fibroblasts(NMCFs)with or without TGF-β1 stimulation.CRLF1 overexpression increased cell viability,collagen production,cell proliferation capacity,and myofibroblast transformation of NMCFs with or without TGF-β1 stimulation,while silencing of CRLF1 had the opposite effects.An inhibitor of the extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway and different inhibitors of TGF-β1 signaling cascades,comprising mothers against decapentaplegic homolog(SMAD)-dependent and SMAD-independent pathways,were applied to investigate the mechanisms involved.CRLF1 exerted its functions by activating the ERK1/2 signaling pathway.Furthermore,the SMAD-dependent pathway,not the SMAD-independent pathway,was responsible for CRLF1 up-regulation in NMCFs treated with TGF-β1.In summary,activation of the TGF-β1/SMAD signaling pathway in cardiac fibrosis increased CRLF1 expression.CRLF1 then aggravated cardiac fibrosis by activating the ERK1/2 signaling pathway.CRLF1 could become a novel potential target for intervention and remedy of cardiac fibrosis. 展开更多
关键词 Cytokine receptor-like factor 1(CRLF1) tgf-β1/smad signaling pathway ERK1/2 signaling pathway Cardiac fibrosis Myofibroblast transformation Extracellular matrix(ECM)
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Pilose antler aqueous extract promotes the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells by stimulating the BMP-2/Smad1, 5/Runx2 signaling pathway 被引量:27
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作者 REN Cong GONG Wei +1 位作者 LI Feng XIE Ming 《Chinese Journal of Natural Medicines》 SCIE CAS CSCD 2019年第10期756-767,共12页
Peptides from Pilose antler aqueous extract(PAAE) have been shown to stimulate the proliferation and differentiation of bone marrow mesenchymal stem cells(BMSCs). However, the underlying molecular mechanisms are not w... Peptides from Pilose antler aqueous extract(PAAE) have been shown to stimulate the proliferation and differentiation of bone marrow mesenchymal stem cells(BMSCs). However, the underlying molecular mechanisms are not well understood. Here, PAAE was isolated and purified to explore the molecular mechanisms underlying PAAE’s effects on BMSCs as well as its osteoprotective effects in ovariectomized rats. Our results showed that PAAE promoted proliferation and differentiation of BMSCs to become osteoblasts by enhancing ALP activity and increasing extracellular matrix mineralization. The trabecular microarchitecture of ovariectomized rats was also found to be protected by PAAE. Quantitative reverse transcription-polymerase chain reaction(Quantitative RT-PCR) results suggest that PAAE also increased the expression of osteogenic markers including, alkaline phosphatase(ALP), runt-related transcription factor 2(Runx2), osteocalcin(OCN), bone morphogenetic protein-2(BMP-2), and collagen I(COL-I). Immunoblotting results indicated that PAAE upregulated the levels of BMP-2 and Runx2 and was associated with Smad1/5 phosphorylation. PAAE A at the concentration of 200μg·mL^-1 showed the strongest effect on proliferation and osteogenic differentiation of BMSCs after 48 h. Using matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF MS), we identified the molecular weight of PAAE A and found that it is less than 3000 Da and showed several significant peaks. In conclusion, PAAE activates the BMP-2/Smad1, 5/Runx2 pathway to induce osteoblastic differentiation and mineralization in BMSCs and can inhibit OVX-induced bone loss. These mechanisms are likely responsible for its therapeutic effect on postmenopausal osteoporosis. 展开更多
关键词 Pilose ANTLER POSTMENOPAUSAL osteoporosis Bone MARROW mesenchymal stem cells BMP-2/smad1 5/Runx2 signaling pathway
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Effect of ursodeoxycholic acid on TGF betal/Smad signaling pathway in rat hepatic stellate cells 被引量:23
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作者 LIANG Tie-jun YUAN Jun-hua +5 位作者 TAN Yan-rong REN Wan-hua HAN Guo-qing ZHANG Jie WANG Lai-cheng QIN Cheng-yong 《Chinese Medical Journal》 SCIE CAS CSCD 2009年第10期1209-1213,共5页
Background Hepatic fibrosis is the key stage of the pathological progress from hepatic injury to cirrhosis. Ursodeoxycholic acid (UDCA) has been known as having significant clinical therapeutic effects on chronic li... Background Hepatic fibrosis is the key stage of the pathological progress from hepatic injury to cirrhosis. Ursodeoxycholic acid (UDCA) has been known as having significant clinical therapeutic effects on chronic liver diseases. Our research aimed to study the effect of UDCA on the signaling pathway of transforming growth factor beta1 (TGFβ1)/Smad and discuss its possible molecular mechanisms of inhibiting hepatic fibrosis. Methods Rat hepatic stellate cells were cultured in vitro and randomly assigned to 4 groups. Group A was control group with only DMEM culture medium applied, and groups B, C, D were experimental groups, with different doses of UDCA (1.0 mmol/L, 0.5 mmol/L and 0.25 mmol/L respectively) added into their DMEM culture medium for further culture of 24 hours and 48 hours. The protein expressions of TGFβ1, TGF type 1 receptor, Smad3, Smad4 and Smad7 were measured by Western blotting, as well as the expressions of TGFβ1, Smad3, Smad7 and cAMP response element (CREB) binding protein (CBP) mRNA by real-time PCR. SPSS 11.5 statistical package was adopted for data analyses. Results Compared with control group, the mRNA expressions of TGFβ1 in the high and middle UDCA dose groups for 24 hours and 48 hours significantly decreased (P 〈0.05), the protein expressions of TGFβ1 in the two above groups for 48 hours and in the high dose group for 24 hours significantly decreased (P 〈0.05). The protein and mRNA expressions of Smad3 in each UDCA dose group for 24 hours and 48 hours significantly decreased, with significant difference among different UDCA dose groups and between that of 24 hours and 48 hours observed (P 〈0.05). The protein and mRNA expressions of Smad7 in the high and middle UDCA dose groups for 24 hours and 48 hours significantly increased. The CBP mRNA expression in each UDCA dose group for 24 hours and 48 hours significantly decreased (P 〈0.05), with significant difference among different UDCA dose groups observed (P 〈0.05). Conclusion UDCA could curb the development of hepatic fibrosis through affecting the signaling pathway of TGFβ1/Smad by inhibiting the expressions of TGFβ1, Smad3 and CBP and increasing the expression of Smad7. 展开更多
关键词 ursodeoxycholic acid hepatic stellate cells transforming growth factor-betal/smad signaling pathway
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The Smad pathway in transforming growth factor-β signaling 被引量:2
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作者 林海燕 王红梅 祝诚 《Science China(Life Sciences)》 SCIE CAS 2003年第5期449-463,共15页
The Smad pathway is involved in transforming growth factor-b (TGF-b) signal transduction. The Smad complex binds with the promoter of target gene to modulate gene transcription. Various transcriptional coactivators an... The Smad pathway is involved in transforming growth factor-b (TGF-b) signal transduction. The Smad complex binds with the promoter of target gene to modulate gene transcription. Various transcriptional coactivators and corepressors associate directly with Smads for appropriate binding of Smads to target promoters and regulation of Smads transcriptional activities. The ultimate degradation of Smads mediated by the ubiquitin-proteasome pathway (UPP) has been established as a mechanism to shut off the Smad pathway. In addition to the Smad pathway, TGF-?can also activate other signaling pathway such as the MAPK pathway. The cross-talk of the Smad pathway with other signaling pathways constitutes an important mechanism for the regulatory network of TGF-b signaling. 展开更多
关键词 tgf-β signaling smad smad pathway MAPK pathway UPP
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Jujuboside A ameliorates tubulointerstitial fibrosis in diabetic mice through down-regulating the YY1/TGF-β1 signaling pathway 被引量:5
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作者 LIU Yang-Yang LI Lin +11 位作者 JI Bei HAO Shi-Long KUANG Xiao-Feng CAO Xin-Yun YUAN Jia-Yu JIANG Zhen-Zhou QIAN Si-Tong WEI Chu-Jing XU Jing YIN Xiao-Xing LU Qian YANG Ting-Ting 《Chinese Journal of Natural Medicines》 SCIE CAS CSCD 2022年第9期656-668,共13页
Diabetic nephropathy(DN)is one of the most common complications of diabetes mellitus,which is characterized in renal tubulointerstitial fibrosis(TIF).The current study was designed to investigate the protective effect... Diabetic nephropathy(DN)is one of the most common complications of diabetes mellitus,which is characterized in renal tubulointerstitial fibrosis(TIF).The current study was designed to investigate the protective effect of Jujuboside A(Ju A)on TIF in type 2 diabetes(T2DM)mice,and explore its underlying anti-fibrosis mechanism.A mouse T2DM model was established using high fat diet(HFD)feeding combined with intraperitoneal injection of streptozotocin(STZ).Then,diabetic mice were treated with Ju A(10,20 and 40 mg·kg^(−1)·d^(−1),i.g.)for 12 weeks.Results showed that administration of Ju A not only down-regulated fasting blood glucose(FBG)levels,but also improved hyperlipidemia and renal function in diabetic mice.Moreover,the reduced ECM accumulation was observed in the renal cortex of Ju A treated diabetic mice,while the TIF progression was also attenuated by Ju A through blocking the epithelial-to-mesenchymal transition(EMT)of renal tubular epithelial cells(RTECs).Further mechanism studies showed that Ju A treatment effectively down-regulated the protein expression and subsequent nuclear translocation of Yin Yang 1(YY1)in the renal cortex of diabetic mice,and reduced the levels of transforming growth factor-β1(TGF-β1)in the serum and renal cortex of Ju A treated mice.According to in vitro studies,the up-regulated YY1/TGF-β1 signaling pathway was restored by Ju A in high glucose(HG)cultured HK-2 cells.Taken together,these findings demonstrated that Ju A can ameliorate the TIF of DN through down-regulating the YY1/TGF-β1 signaling pathway. 展开更多
关键词 Diabetic nephropathy Jujuboside A Tubulointerstitial fibrosis Extracellular matrix YY1/tgf-β1 signaling pathway
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Inhibitory effects of oxyresveratrol on ERK and Smad1/2 phosphorylation and HSC activation in preventing carbon tetrachloride-induced rat liver fibrosis 被引量:1
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作者 Guliang Yang Jianfeng Zhan +4 位作者 Yiwen Yang Li Yuan Peilei Wang Chi-Tang Ho Shiming Li 《Food Science and Human Wellness》 SCIE 2021年第1期6-12,共7页
Oxyresveratrol(ORes,trans-2,4,3′,5′-tetrahydroxy stilbene)naturally exists in mulberry,grapes,peanuts and other plants.It belongs to stilbene polyphenolic family and has an extra hydroxyl group at 2-position compari... Oxyresveratrol(ORes,trans-2,4,3′,5′-tetrahydroxy stilbene)naturally exists in mulberry,grapes,peanuts and other plants.It belongs to stilbene polyphenolic family and has an extra hydroxyl group at 2-position comparing with resveratrol(Res).Hence,ORes has stronger antioxidant activity than resveratrol.In present study,we employed a rat hepatic fibrosis model induced by carbon tetrachloride(CCl_(4))and administrated ORes via gavage feeding to study the protective effects and potential mechanisms of ORes against hepatic fibrosis.We demonstrated that rat liver oxidative damage induced by CCl_(4)was significantly alleviated after ORes feeding.Furthermore,the mRNA transcription levels ofα-smooth muscle actinn(˛-SMA),desmin,and two MMPs(MMP2 and MMP9)were reduced and the expression levels of transforming growth factorβ1(TGF-β1),p-small mother against decapen-taplegic protein(Smad)1/2 and p-extracellular signal-regulated kinases(ERK)1/2 in the liver tissue down-regulated dramatically.In a parallel study with Res,ORes showed more efficacious protective effect than Res against rat liver fibrosis,which is attributed to extended conjugation system due to the extra hydroxyl group at 2-position on ORes making it more electron-rich and susceptible to oxidation than Res.Therefore,dietary consumption of mulberry and other fruits containing ORes may be beneficial in the prevention of liver fibrosis. 展开更多
关键词 OXYRESVERATROL Hepatic fibrosis Oxidative stress tgf-β/smad/ERK signaling pathway
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Celastrol Protects TGF-β1-induced Endothelial-mesenchymal Transition 被引量:1
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作者 龚斐 赵芳 干学东 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2017年第2期185-190,共6页
The endothelial-to-mesenchymal transition(End MT) in endothelial cells contributes to the development of cardiac fibrosis,ultimately leading to cardiac remodeling.In this study,the effects and molecular mechanisms o... The endothelial-to-mesenchymal transition(End MT) in endothelial cells contributes to the development of cardiac fibrosis,ultimately leading to cardiac remodeling.In this study,the effects and molecular mechanisms of celastrol(CEL) on transforming growth factor-β1(TGF-β1)-induced End MT in human umbilical vein endothelial(HUVEC-12) cells were investigated.The presented data demonstrated that CEL significantly blocked the morphology change of HUVEC-12 cells induced by TGF-β1 without cell cytotoxicity.In accordance with these findings,CEL blocked TGF-β1-induced EndM T as evidenced by the inhibition of the mesenchymal markers,including collagen Ⅰ,Ⅲ,α-SMA,fibronectin m RNA expression,and the increase in the m RNA expression of endothelial cell marker CD31.These changes were also confirmed by double immunofluorescence staining of CD31 and vimentin.The in vitro scratch assay showed that CEL inhibited the migration capacity of the transitioned endothelial cells induced by TGF-β1.Further experiments showed that the beneficial effect of CEL on blocking the End MT in HUVEC-12 cells was associated with the suppression of the TGF-β1/Smads signalling pathway,which was also confirmed by the inhibition of its downstream transcription factor snail1,twist1,twist2,ZEB1 and ZEB2.These results indicate that CEL blocks TGF-β1-induced End MT through TGF-β1/Smads signalling pathway and suggest that it may be a feasible therapy for cardiac fibrosis diseases. 展开更多
关键词 endothelial-mesenchymal transition celastrol endothelium tgf-β1/smads signaling pathway cardiac fibrosis
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