Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may de...Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types involved.Voltage-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related diseases.However,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear.In this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from mice.We found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 expression.Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons.These findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions.Thus,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.展开更多
BACKGROUND: Previous studies have shown that transforming growth factor-beta 1 (TGF-beta 1) is the most potent means of stimulating liver fibrogenesis by myofibroblast-like cells derived from hepatic stellate cells. T...BACKGROUND: Previous studies have shown that transforming growth factor-beta 1 (TGF-beta 1) is the most potent means of stimulating liver fibrogenesis by myofibroblast-like cells derived from hepatic stellate cells. Thus, TGF-beta 1 could be a target for treating hepatic fibrosis. This study aimed to investigate the inhibitory effects of specific TGF-beta 1 small interference RNA (siRNA) on immune hepatic fibrosis induced by Concanavalin A (Con A) in mice. METHODS: Three short hairpin RNAs targeting different positions of TGF-beta 1 were designed and cloned to the plasmid pGenesil-1 to obtain three recombinant expression vectors (pGenesil-TGF-beta 1-ml, pGenesil-TGF-beta 1-m2 and pGenesil-TGF-beta 1-m3). Thirty male Kunming mice were randomly divided into 6 groups: normal, model, control, and three treatment groups. The immune hepatic fibrosis models were constructed by injecting Con A via the tail vein at 8 mg/kg per week for 6 weeks. At weeks 2, 4 and 6, pGenesil-TGF-beta 1-ml, pGenesil-TGF-beta 1-m2 or pGenesi1-TGF-beta 1-m3 was injected by a hydrodynamics-based transfection method via the tail vein at 0.8 ml/10 g within 24 hours after injection of Con A in each of the three treatment groups. The mice in the control group were injected with control plasmid pGenesil-HK at the same dose. All mice were sacrificed at week 7. The levels of hydroxyproline in liver tissue were determined by biochemistry. Liver histopathology was assessed by Van Gieson staining. The expression levels and localization of TGF-beta 1, Smad3, and Smad7 in liver tissue were detected by immunohistochemistry. The expression of TGF-beta 1, Smad3, Smad7 and alpha-smooth muscle actin (alpha-SMA) mRNAs in the liver were assessed by semi-quantitative RT-PCR. RESULTS: The levels of hydroxyproline in the liver tissue of the treatment groups were lower than those of the model group (P<0.01). Histopathologic assay showed that liver fibrogenesis was clearly improved in the treatment groups compared with the model group. The expression levels of TGF-beta 1 and Smad3 of liver tissue were also markedly lower in the treatment groups than in the model group (P<0.01), while the levels of Smad7 were higher in the treatment groups than in the model group (P<0.01). RT-PCR further showed that the expression of TGF-beta 1, Smad3 and alpha-SMA mRNA was significantly inhibited in the treatment groups compared with the model group, while the levels of Smad7 were increased. There was no difference in the above parameters among the three treatment groups or between the control and model groups (P>0.05), but the inhibitory effect of pGenesil-TGF-beta 1-ml was the highest among the treatment groups. CONCLUSIONS: Specific siRNA targeting of TGF-beta 1 markedly inhibited the fibrogenesis of immune hepatic fibrosis induced by Con A in mice. The anti-fibrosis mechanisms of siRNAs may be associated with the down-regulation of TGF-beta 1, Smad3 and alpha-SMA expression and up-regulation of Smad7 expression in liver tissue, which resulted in suppressing the activation of hepatic stellate cells. (Hepatobiliary Pancreat Dis Int 2009; 8: 300-308)展开更多
Transforming growth factor-beta(TGF-β)is a multifunctional cytokine that performs a dual role as a tumor suppressor and tumor promoter during cancer progression.Among different ligands of the TGF-βfamily,TGF-β1 mod...Transforming growth factor-beta(TGF-β)is a multifunctional cytokine that performs a dual role as a tumor suppressor and tumor promoter during cancer progression.Among different ligands of the TGF-βfamily,TGF-β1 modulates most of its biological outcomes.Despite the abundant expression of TGF-β1 in the liver,steatosis to hepatocellular carcinoma(HCC)progression triggers elevated TGF-β1 levels,contributing to poor prognosis and survival.Additionally,elevated TGF-β1 levels in the tumor microenvironment create an immunosuppressive stage via various mechanisms.TGF-β1 has a prime role as a diagnostic and prognostic biomarker in HCC.Moreover,TGF-β1 is widely studied as a therapeutic target either as monotherapy or combined with immune checkpoint inhibitors.This review provides clinical relevance and up-to-date information regarding the potential of TGF-β1 in diagnosis,prognosis,and therapy against HCC.展开更多
The expression of the anti-apoptotic molecules Bcl-2 and transforming growth factor-beta 1 is known to confer protective effects on the cerebral ischemia-reperfusion injury.The current study investigated the expressio...The expression of the anti-apoptotic molecules Bcl-2 and transforming growth factor-beta 1 is known to confer protective effects on the cerebral ischemia-reperfusion injury.The current study investigated the expression levels of Bcl-2 and transforming growth factor-beta 1 in response to multiple pre-ischemia electro-acupuncture at acupoints Zusanli（ST36）and Fengchi（GB20） stimulation.Rats were divided into five groups：uninjured,control,non-acupoint,GB20 and ST36. Rats in the non-acupoint,GB20 and ST36 groups received 30 minutes（3 times or 18 times）of electro-acupuncture stimulation before experimental cerebral ischemia was induced.Bcl-2 and transforming growth factor-beta 1 were found to be significantly increased in the ST36 groups with either 3 or 18 electro-acupuncture treatments（P〈0.05）.The production was higher with 18 electro-acupuncture treatments in the ST36 groups（P〈0.05）.In the GB20 groups,significant increase was only observed in transforming growth factor-beta 1 with 18 electro-acupuncture treatments（P〈0.05）.No significant elevation of the level of transforming growth factor-beta 1 was observed in the non-acupoint groups.However,the production of Bcl-2 increased with 18 treatments in the non-acupoint groups（P〈0.05）.The data suggest that multiple pre-ischemia electro-acupuncture at ST36 was effective in conferring neuroprotective effect on the brain by means of upregulation of Bcl-2 and transforming growth factor-beta 1 and the effect was increase with the number of treatment.展开更多
AIM： To study the influence of HBcAg on the expression of transforming growth factor-beta 1 （TGF-131） in liver tissue of low-grade chronic hepatitis B （CHB） patients. METHODS： The expression of T（3F-β1 and HBc...AIM： To study the influence of HBcAg on the expression of transforming growth factor-beta 1 （TGF-131） in liver tissue of low-grade chronic hepatitis B （CHB） patients. METHODS： The expression of T（3F-β1 and HBcAg in liver samples from 93 low-grade CHB patients was detected by immunohistochemistry and valuated by semi-quantitative scoring. RESULTS： In the 93 low-grade CHB patients, HBcAg was expressed in cell plasma but not in the liver tissue. There was no significant difference between the two groups. CONCLUSION： The expression of TGF-β1 is not related with HBcAg expressed as plasma type in the tissues of low-grade CHB patients.展开更多
BACKGROUND The role of Tousled-like kinase 1(TLK1)in in gastric cancer(GC)remains unclear.AIM To investigate the expression,biological function,and underlying mechanisms of TLK1 in GC.METHODS We measured TLK1 protein ...BACKGROUND The role of Tousled-like kinase 1(TLK1)in in gastric cancer(GC)remains unclear.AIM To investigate the expression,biological function,and underlying mechanisms of TLK1 in GC.METHODS We measured TLK1 protein expression levels and localized TLK1 in GC cells and tissues by western blot and immunofluorescence,respectively.We transfected various GC cells with lentiviruses to create TLK1 overexpression and knockdown lines and established the functional roles of TLK1 through in vitro colony formation,5-ethynyl-2`-deoxyuridine,and Transwell assays as well as flow cytometry.We applied bioinformatics to elucidate the signaling pathways associated with TLK1.We performed in vivo validation of TLK1 functions by inducing subcutaneous xenograft tumors in nude mice.RESULTS TLK1 was significantly upregulated in GC cells and tissues compared to their normal counterparts and was localized mainly to the nucleus.TLK1 knockdown significantly decreased colony formation,proliferation,invasion,and migration but increased apoptosis in GC cells.TLK1 overexpression had the opposite effects.Bioinformatics revealed,and subsequent experiments verified,that the tumor growth factor-beta signaling pathway was implicated in TLK1-mediated GC progression.The in vivo assays confirmed that TLK1 promotes tumorigenesis in GC.CONCLUSION The findings of the present study indicated that TLK1 plays a crucial role in GC progression and is,therefore,promising as a therapeutic target against this disease.展开更多
Background: Cyclooxygenase-2 (COX-2) and transforming growth factor-beta1 (TGF-β1) are modulated in variety cancers including Hepatocellular carcinoma (HCC). However, there is a paucity of data concerning their role ...Background: Cyclooxygenase-2 (COX-2) and transforming growth factor-beta1 (TGF-β1) are modulated in variety cancers including Hepatocellular carcinoma (HCC). However, there is a paucity of data concerning their role in the pathologic process of recurrence of HCC following hepatectomy. We herein assessed the role of the hepatic expression of COX-2 and TGF-β as predictors for patients with early recurrence within 2 years of HCC diagnosis. Methods: Sixty patients with HCC who underwent curative hepatectomy between 2000 and 2003 were entered in the present study. The immunoreactivity and distribution patterns of COX-2 and TGF-β1 were examined in both the HCC and the adjacent nonHCC tissues of the liver. Risk factors of tumor recurrence within 2 years, including COX-2 and TGF-β1 expression, were investigated by univariate and multivariate analyses. Results: Among 60 patients, 31 patients had early recurrences within 2 years and 14 patients recurred after 2 years following surgery. Patients with low COX-2 expression in the HCC tissues and adjacent nonHCC tissues had favorable disease-free survival (p = 0.002 and p β1 expression in the nonHCC tissues had also longer disease-free survival (p = 0.045). Based on the expression patterns of COX-2 and TGF-β1, patients with low COX-2 and positive TGF-β1 expression in the nonHCC tissues had favorable overall and disease-free survival (p β1 signaling in nontumor tissues suggested high risk of recurrence and poor survival to the HCC patients following hepatectomy.展开更多
Objective: In women with pelvic organ prolapse (POP), decreased expression of transforming growth factor-beta 1 (TGF-β1) has been shown in POP tissues. However, no studies have evaluated plasma TGF-β1 levels in pati...Objective: In women with pelvic organ prolapse (POP), decreased expression of transforming growth factor-beta 1 (TGF-β1) has been shown in POP tissues. However, no studies have evaluated plasma TGF-β1 levels in patients with POP, so it is unknown whether they are also changed or not. Therefore, we compared plasma TGF-β1 levels in women with and without POP. Methods: Participants were 49 women with POP and 23 healthy control women. All participants were postmenopausal. We measured plasma TGF-β1 and compared data between patients with POP and controls, and between patients with uterine prolapse (UP, n = 19) and those with a cystocele (CC, n = 30). In addition, in patients, we assessed the POP quantification system (POP-Q) stage. Results: Plasma TGF-β1 levels were significantly lower in patients than in healthy controls. POP-Q stage was not significantly different between the UP and CC subgroups, but POP-Q stage IV was diagnosed in 63% of patients with UP and 7% of those with CC. Plasma TGF-β1 levels were significantly lower in the CC subgroup than in the UP subgroup. Conclusion: Plasma TGF-β1 is decreased in POP. It remains unclear whether the lower levels indicate a reduction in systemic TGF-β1 activity, but they can be assumed to reflect reduced TGF-β1 expression in POP tissues.展开更多
AIM: To characterize the expression of members of the transforming growth factor-beta (TGF-β)/Smad/ connective tissue growth factor (CTGF) signaling pathway in the tissue of benign biliary stricture, and to investiga...AIM: To characterize the expression of members of the transforming growth factor-beta (TGF-β)/Smad/ connective tissue growth factor (CTGF) signaling pathway in the tissue of benign biliary stricture, and to investigate the effect of TGF-β signaling pathway in the pathogenesis of benign biliary stricture. METHODS: Paraffin embedded materials from 23 cases of benign biliary stricture were analyzed for members of the TGF-β/Smad/CTGF signaling pathway. TGF-β_1, TβRⅠ, TβRⅡ, Smad4, Smad7 and CTGF protein were detected by immunohistochemical strepto-advidinbiotin complex method, and CTGF mRNA was evaluated by hybridization in situ, while 6 cases of normal bile duct served as controls. The percentages of positive cells were counted. The correlation between TGF-β_1, Smad4 and CTGF was analyzed. RESULTS: The positive expression ratios of TGF-β_1, TβRⅠ , TβRⅡ , Smad4, CTGF and CTGF mRNA in 23 cases with benign biliary stricture were 91.3%, 82.6%, 87.0%, 78.3%, 82.6% and 65.2%, respectively, signifi cantly higher than that in 6 cases of normal bile duct respectively (vs 33.3%, 16.7%, 50.0%, 33.3%, 50.0%, 16.7%, respectively, P < 0.05). The positiveexpression ratio of Smad7 in cases with benign biliary stricture was 70.0%, higher than that in normal bile duct, but this difference is not statistically signifi cant 70.0% vs 50%, P > 0.05). There was a positive correlation between positive expression of TGF-β_1, Smad4 and CTGF in cases with benign biliary stricture. CONCLUSION: The high expression of TGF-β/Smad/ CTGF signaling pathway plays an important role in the pathogenesis of benign biliary stricture.展开更多
Recently,phosphatase and tensin homolog deleted on chromosome 10（PTEN） is suggested as a new agent in the fighting against fibrogenesis.In tumor,DJ-1 is identified as a negative regulator of PTEN.But the expression ...Recently,phosphatase and tensin homolog deleted on chromosome 10（PTEN） is suggested as a new agent in the fighting against fibrogenesis.In tumor,DJ-1 is identified as a negative regulator of PTEN.But the expression of DJ-1 and the regulation of PTEN in fibrosis are unclear.Renal fibrosis was induced in 5/6 subtotal nephrectomy rat model.Human proximal tubular epithelial cells（HKC） were treated with transforming growth factor-beta 1（TGF-β1）,or transfected with DJ-1 or PTEN.Confocal microscope was used to investigate the localization of DJ-1 and PTEN.The selective phosphoinositide-3 kinase（PI3K） inhibitor,LY294002,was administered to inhibit PI3K pathway.The DJ-1 and PTEN expression,markers of epithelial-mesenchymal transition（EMT） and Akt phosphorylation were measured by RT-PCR,Western blotting or immunocytochemistry.In vitro,after HKC cells were stimulated with 10 ng/mL TGF-β1 for 72 h,the expression of DJ-1 was increased,and that of PTEN was decreased.In vivo,the same results were identified in 5/6-nephrectomized rats.In normal HKC cells,most of DJ-1 protein localized in cytoplasm,and little in nucleus.TGF-β1 upregulated DJ-1 expression in both cytoplasma and nuclei.In contrary,TGF-β1 emptied cytoplasmic PTEN protein into nucleus.Overexpression of DJ-1 decreased the expression of PTEN,promoted the activation of Akt and the expression of vimentin,and also led to the loss of cytoplasmic PTEN.Contrarily,overexpression of PTEN protected HKC cells from TGF-β1-induced EMT.In conclusion,DJ-1 is upregulated in renal fibrosis and DJ-1 mediates EMT by suppressing cytoplasmic PTEN expression and Akt activation.展开更多
AIM:To determine the expression and clinical significance of transcriptional intermediary factor 1 gamma (TIF1γ),Smad4 and transforming growth factor-beta (TGFβR) across a spectrum representing colorectal cancer (CR...AIM:To determine the expression and clinical significance of transcriptional intermediary factor 1 gamma (TIF1γ),Smad4 and transforming growth factor-beta (TGFβR) across a spectrum representing colorectal cancer (CRC) development.METHODS:Tissue microarrays were prepared from archival paraffin embedded tissue,including 51 colorectal carcinomas,25 tubular adenomas (TA) and 26 HPs,each with matched normal colonic epithelium.Immunohistochemistry was performed using antibodies against TIF1γ,Smad4 and TGFβ RⅡ.The levels of expression were scored semi-quantitatively (score 0-3 or loss and retention for Smad4).RESULTS:Overexpression of TIF1γ was detected in 5/26 (19%) HP;however,it was seen in a significantly higher proportion of neoplasms,15/25 (60%) TAs and 24/51 (47%) CRCs (P<0.05).Normal colonic mucosa,HP,and TAs showed strong Smad4 expression,while its expression was absent in 22/51 (43%) CRCs.Over-expression of TGFβ RⅡ was more commonly seen in neoplasms,13/25 (52%) TAs and 29/51 (57%) CRCs compared to 9/26 (35%) HP (P<0.05).Furthermore,there was a correlation between TIF1γ overexpression and Smad4 loss in CRC (Kendall tau rank correlation value=0.35,P<0.05).The levels of TIF1γ overexpression were significantly higher in stage Ⅲ than in stage Ⅰ and Ⅱ CRC (P<0.05).CONCLUSION:The findings suggest that over-expression of TIF1γ occurs in early stages of colorectal carcinogenesis,is inversely related with Smad4 loss,and may be a prognostic indicator for poor outcome.展开更多
基金supported by the Natural Science Foundation of Guangdong Province,Nos.2019A1515010649(to WC),2022A1515012044(to JS)the China Postdoctoral Science Foundation,No.2018M633091(to JS).
文摘Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types involved.Voltage-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related diseases.However,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear.In this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from mice.We found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 expression.Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons.These findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions.Thus,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.
文摘BACKGROUND: Previous studies have shown that transforming growth factor-beta 1 (TGF-beta 1) is the most potent means of stimulating liver fibrogenesis by myofibroblast-like cells derived from hepatic stellate cells. Thus, TGF-beta 1 could be a target for treating hepatic fibrosis. This study aimed to investigate the inhibitory effects of specific TGF-beta 1 small interference RNA (siRNA) on immune hepatic fibrosis induced by Concanavalin A (Con A) in mice. METHODS: Three short hairpin RNAs targeting different positions of TGF-beta 1 were designed and cloned to the plasmid pGenesil-1 to obtain three recombinant expression vectors (pGenesil-TGF-beta 1-ml, pGenesil-TGF-beta 1-m2 and pGenesil-TGF-beta 1-m3). Thirty male Kunming mice were randomly divided into 6 groups: normal, model, control, and three treatment groups. The immune hepatic fibrosis models were constructed by injecting Con A via the tail vein at 8 mg/kg per week for 6 weeks. At weeks 2, 4 and 6, pGenesil-TGF-beta 1-ml, pGenesil-TGF-beta 1-m2 or pGenesi1-TGF-beta 1-m3 was injected by a hydrodynamics-based transfection method via the tail vein at 0.8 ml/10 g within 24 hours after injection of Con A in each of the three treatment groups. The mice in the control group were injected with control plasmid pGenesil-HK at the same dose. All mice were sacrificed at week 7. The levels of hydroxyproline in liver tissue were determined by biochemistry. Liver histopathology was assessed by Van Gieson staining. The expression levels and localization of TGF-beta 1, Smad3, and Smad7 in liver tissue were detected by immunohistochemistry. The expression of TGF-beta 1, Smad3, Smad7 and alpha-smooth muscle actin (alpha-SMA) mRNAs in the liver were assessed by semi-quantitative RT-PCR. RESULTS: The levels of hydroxyproline in the liver tissue of the treatment groups were lower than those of the model group (P<0.01). Histopathologic assay showed that liver fibrogenesis was clearly improved in the treatment groups compared with the model group. The expression levels of TGF-beta 1 and Smad3 of liver tissue were also markedly lower in the treatment groups than in the model group (P<0.01), while the levels of Smad7 were higher in the treatment groups than in the model group (P<0.01). RT-PCR further showed that the expression of TGF-beta 1, Smad3 and alpha-SMA mRNA was significantly inhibited in the treatment groups compared with the model group, while the levels of Smad7 were increased. There was no difference in the above parameters among the three treatment groups or between the control and model groups (P>0.05), but the inhibitory effect of pGenesil-TGF-beta 1-ml was the highest among the treatment groups. CONCLUSIONS: Specific siRNA targeting of TGF-beta 1 markedly inhibited the fibrogenesis of immune hepatic fibrosis induced by Con A in mice. The anti-fibrosis mechanisms of siRNAs may be associated with the down-regulation of TGF-beta 1, Smad3 and alpha-SMA expression and up-regulation of Smad7 expression in liver tissue, which resulted in suppressing the activation of hepatic stellate cells. (Hepatobiliary Pancreat Dis Int 2009; 8: 300-308)
基金Supported by the Amrita Vishwa Vidyapeetham SEED grant (K-PHAR-22-662)
文摘Transforming growth factor-beta(TGF-β)is a multifunctional cytokine that performs a dual role as a tumor suppressor and tumor promoter during cancer progression.Among different ligands of the TGF-βfamily,TGF-β1 modulates most of its biological outcomes.Despite the abundant expression of TGF-β1 in the liver,steatosis to hepatocellular carcinoma(HCC)progression triggers elevated TGF-β1 levels,contributing to poor prognosis and survival.Additionally,elevated TGF-β1 levels in the tumor microenvironment create an immunosuppressive stage via various mechanisms.TGF-β1 has a prime role as a diagnostic and prognostic biomarker in HCC.Moreover,TGF-β1 is widely studied as a therapeutic target either as monotherapy or combined with immune checkpoint inhibitors.This review provides clinical relevance and up-to-date information regarding the potential of TGF-β1 in diagnosis,prognosis,and therapy against HCC.
基金supported by the Niche Area Grant of the Hong Kong Polytechnic University through the projects JBB71 and BB8V
文摘The expression of the anti-apoptotic molecules Bcl-2 and transforming growth factor-beta 1 is known to confer protective effects on the cerebral ischemia-reperfusion injury.The current study investigated the expression levels of Bcl-2 and transforming growth factor-beta 1 in response to multiple pre-ischemia electro-acupuncture at acupoints Zusanli（ST36）and Fengchi（GB20） stimulation.Rats were divided into five groups：uninjured,control,non-acupoint,GB20 and ST36. Rats in the non-acupoint,GB20 and ST36 groups received 30 minutes（3 times or 18 times）of electro-acupuncture stimulation before experimental cerebral ischemia was induced.Bcl-2 and transforming growth factor-beta 1 were found to be significantly increased in the ST36 groups with either 3 or 18 electro-acupuncture treatments（P〈0.05）.The production was higher with 18 electro-acupuncture treatments in the ST36 groups（P〈0.05）.In the GB20 groups,significant increase was only observed in transforming growth factor-beta 1 with 18 electro-acupuncture treatments（P〈0.05）.No significant elevation of the level of transforming growth factor-beta 1 was observed in the non-acupoint groups.However,the production of Bcl-2 increased with 18 treatments in the non-acupoint groups（P〈0.05）.The data suggest that multiple pre-ischemia electro-acupuncture at ST36 was effective in conferring neuroprotective effect on the brain by means of upregulation of Bcl-2 and transforming growth factor-beta 1 and the effect was increase with the number of treatment.
基金Supported by the Beijing Science and Technology Commission,No.H020920020290
文摘AIM： To study the influence of HBcAg on the expression of transforming growth factor-beta 1 （TGF-131） in liver tissue of low-grade chronic hepatitis B （CHB） patients. METHODS： The expression of T（3F-β1 and HBcAg in liver samples from 93 low-grade CHB patients was detected by immunohistochemistry and valuated by semi-quantitative scoring. RESULTS： In the 93 low-grade CHB patients, HBcAg was expressed in cell plasma but not in the liver tissue. There was no significant difference between the two groups. CONCLUSION： The expression of TGF-β1 is not related with HBcAg expressed as plasma type in the tissues of low-grade CHB patients.
基金Supported by the Key Programs of the Educational Commission of Anhui Province,No.2023AH053313the Research Project of Higher Education in Anhui Province in 2022,No.2022AH051192.
文摘BACKGROUND The role of Tousled-like kinase 1(TLK1)in in gastric cancer(GC)remains unclear.AIM To investigate the expression,biological function,and underlying mechanisms of TLK1 in GC.METHODS We measured TLK1 protein expression levels and localized TLK1 in GC cells and tissues by western blot and immunofluorescence,respectively.We transfected various GC cells with lentiviruses to create TLK1 overexpression and knockdown lines and established the functional roles of TLK1 through in vitro colony formation,5-ethynyl-2`-deoxyuridine,and Transwell assays as well as flow cytometry.We applied bioinformatics to elucidate the signaling pathways associated with TLK1.We performed in vivo validation of TLK1 functions by inducing subcutaneous xenograft tumors in nude mice.RESULTS TLK1 was significantly upregulated in GC cells and tissues compared to their normal counterparts and was localized mainly to the nucleus.TLK1 knockdown significantly decreased colony formation,proliferation,invasion,and migration but increased apoptosis in GC cells.TLK1 overexpression had the opposite effects.Bioinformatics revealed,and subsequent experiments verified,that the tumor growth factor-beta signaling pathway was implicated in TLK1-mediated GC progression.The in vivo assays confirmed that TLK1 promotes tumorigenesis in GC.CONCLUSION The findings of the present study indicated that TLK1 plays a crucial role in GC progression and is,therefore,promising as a therapeutic target against this disease.
文摘Background: Cyclooxygenase-2 (COX-2) and transforming growth factor-beta1 (TGF-β1) are modulated in variety cancers including Hepatocellular carcinoma (HCC). However, there is a paucity of data concerning their role in the pathologic process of recurrence of HCC following hepatectomy. We herein assessed the role of the hepatic expression of COX-2 and TGF-β as predictors for patients with early recurrence within 2 years of HCC diagnosis. Methods: Sixty patients with HCC who underwent curative hepatectomy between 2000 and 2003 were entered in the present study. The immunoreactivity and distribution patterns of COX-2 and TGF-β1 were examined in both the HCC and the adjacent nonHCC tissues of the liver. Risk factors of tumor recurrence within 2 years, including COX-2 and TGF-β1 expression, were investigated by univariate and multivariate analyses. Results: Among 60 patients, 31 patients had early recurrences within 2 years and 14 patients recurred after 2 years following surgery. Patients with low COX-2 expression in the HCC tissues and adjacent nonHCC tissues had favorable disease-free survival (p = 0.002 and p β1 expression in the nonHCC tissues had also longer disease-free survival (p = 0.045). Based on the expression patterns of COX-2 and TGF-β1, patients with low COX-2 and positive TGF-β1 expression in the nonHCC tissues had favorable overall and disease-free survival (p β1 signaling in nontumor tissues suggested high risk of recurrence and poor survival to the HCC patients following hepatectomy.
文摘Objective: In women with pelvic organ prolapse (POP), decreased expression of transforming growth factor-beta 1 (TGF-β1) has been shown in POP tissues. However, no studies have evaluated plasma TGF-β1 levels in patients with POP, so it is unknown whether they are also changed or not. Therefore, we compared plasma TGF-β1 levels in women with and without POP. Methods: Participants were 49 women with POP and 23 healthy control women. All participants were postmenopausal. We measured plasma TGF-β1 and compared data between patients with POP and controls, and between patients with uterine prolapse (UP, n = 19) and those with a cystocele (CC, n = 30). In addition, in patients, we assessed the POP quantification system (POP-Q) stage. Results: Plasma TGF-β1 levels were significantly lower in patients than in healthy controls. POP-Q stage was not significantly different between the UP and CC subgroups, but POP-Q stage IV was diagnosed in 63% of patients with UP and 7% of those with CC. Plasma TGF-β1 levels were significantly lower in the CC subgroup than in the UP subgroup. Conclusion: Plasma TGF-β1 is decreased in POP. It remains unclear whether the lower levels indicate a reduction in systemic TGF-β1 activity, but they can be assumed to reflect reduced TGF-β1 expression in POP tissues.
基金The grant from Shaanxi Science and Technology Project, No. 2002K10-G8
文摘AIM: To characterize the expression of members of the transforming growth factor-beta (TGF-β)/Smad/ connective tissue growth factor (CTGF) signaling pathway in the tissue of benign biliary stricture, and to investigate the effect of TGF-β signaling pathway in the pathogenesis of benign biliary stricture. METHODS: Paraffin embedded materials from 23 cases of benign biliary stricture were analyzed for members of the TGF-β/Smad/CTGF signaling pathway. TGF-β_1, TβRⅠ, TβRⅡ, Smad4, Smad7 and CTGF protein were detected by immunohistochemical strepto-advidinbiotin complex method, and CTGF mRNA was evaluated by hybridization in situ, while 6 cases of normal bile duct served as controls. The percentages of positive cells were counted. The correlation between TGF-β_1, Smad4 and CTGF was analyzed. RESULTS: The positive expression ratios of TGF-β_1, TβRⅠ , TβRⅡ , Smad4, CTGF and CTGF mRNA in 23 cases with benign biliary stricture were 91.3%, 82.6%, 87.0%, 78.3%, 82.6% and 65.2%, respectively, signifi cantly higher than that in 6 cases of normal bile duct respectively (vs 33.3%, 16.7%, 50.0%, 33.3%, 50.0%, 16.7%, respectively, P < 0.05). The positiveexpression ratio of Smad7 in cases with benign biliary stricture was 70.0%, higher than that in normal bile duct, but this difference is not statistically signifi cant 70.0% vs 50%, P > 0.05). There was a positive correlation between positive expression of TGF-β_1, Smad4 and CTGF in cases with benign biliary stricture. CONCLUSION: The high expression of TGF-β/Smad/ CTGF signaling pathway plays an important role in the pathogenesis of benign biliary stricture.
基金supported by a grant from National Natural Sciences Foundation of China (No. 30800525)
文摘Recently,phosphatase and tensin homolog deleted on chromosome 10（PTEN） is suggested as a new agent in the fighting against fibrogenesis.In tumor,DJ-1 is identified as a negative regulator of PTEN.But the expression of DJ-1 and the regulation of PTEN in fibrosis are unclear.Renal fibrosis was induced in 5/6 subtotal nephrectomy rat model.Human proximal tubular epithelial cells（HKC） were treated with transforming growth factor-beta 1（TGF-β1）,or transfected with DJ-1 or PTEN.Confocal microscope was used to investigate the localization of DJ-1 and PTEN.The selective phosphoinositide-3 kinase（PI3K） inhibitor,LY294002,was administered to inhibit PI3K pathway.The DJ-1 and PTEN expression,markers of epithelial-mesenchymal transition（EMT） and Akt phosphorylation were measured by RT-PCR,Western blotting or immunocytochemistry.In vitro,after HKC cells were stimulated with 10 ng/mL TGF-β1 for 72 h,the expression of DJ-1 was increased,and that of PTEN was decreased.In vivo,the same results were identified in 5/6-nephrectomized rats.In normal HKC cells,most of DJ-1 protein localized in cytoplasm,and little in nucleus.TGF-β1 upregulated DJ-1 expression in both cytoplasma and nuclei.In contrary,TGF-β1 emptied cytoplasmic PTEN protein into nucleus.Overexpression of DJ-1 decreased the expression of PTEN,promoted the activation of Akt and the expression of vimentin,and also led to the loss of cytoplasmic PTEN.Contrarily,overexpression of PTEN protected HKC cells from TGF-β1-induced EMT.In conclusion,DJ-1 is upregulated in renal fibrosis and DJ-1 mediates EMT by suppressing cytoplasmic PTEN expression and Akt activation.
基金Supported by Department of Pathology Research Fund,NYU School of Medicine,New York,NY 10016,United States
文摘AIM:To determine the expression and clinical significance of transcriptional intermediary factor 1 gamma (TIF1γ),Smad4 and transforming growth factor-beta (TGFβR) across a spectrum representing colorectal cancer (CRC) development.METHODS:Tissue microarrays were prepared from archival paraffin embedded tissue,including 51 colorectal carcinomas,25 tubular adenomas (TA) and 26 HPs,each with matched normal colonic epithelium.Immunohistochemistry was performed using antibodies against TIF1γ,Smad4 and TGFβ RⅡ.The levels of expression were scored semi-quantitatively (score 0-3 or loss and retention for Smad4).RESULTS:Overexpression of TIF1γ was detected in 5/26 (19%) HP;however,it was seen in a significantly higher proportion of neoplasms,15/25 (60%) TAs and 24/51 (47%) CRCs (P<0.05).Normal colonic mucosa,HP,and TAs showed strong Smad4 expression,while its expression was absent in 22/51 (43%) CRCs.Over-expression of TGFβ RⅡ was more commonly seen in neoplasms,13/25 (52%) TAs and 29/51 (57%) CRCs compared to 9/26 (35%) HP (P<0.05).Furthermore,there was a correlation between TIF1γ overexpression and Smad4 loss in CRC (Kendall tau rank correlation value=0.35,P<0.05).The levels of TIF1γ overexpression were significantly higher in stage Ⅲ than in stage Ⅰ and Ⅱ CRC (P<0.05).CONCLUSION:The findings suggest that over-expression of TIF1γ occurs in early stages of colorectal carcinogenesis,is inversely related with Smad4 loss,and may be a prognostic indicator for poor outcome.
