Objective:To explore the effect of Cassia fistula on collagenⅡ-induced arthritis in rats.Methods:The effect of 250 and 500 mg/kg chloroform and hydroalcoholic extract of Cassia fistula leaf on collagenⅡ-induced arth...Objective:To explore the effect of Cassia fistula on collagenⅡ-induced arthritis in rats.Methods:The effect of 250 and 500 mg/kg chloroform and hydroalcoholic extract of Cassia fistula leaf on collagenⅡ-induced arthritis was investigated by evaluating paw volume,arthritis index,spleen index,and biochemical parameters.Histopathological analysis and docking study were also performed.Results:A dose-dependent reduction in paw volume,arthritic index,and spleen index was observed following oral administration of the chloroform and hydroalcoholic extracts.Treatment with Cassia fistula extracts reduced tumor necrosis factor-α,interleukin(IL)-1β,IL-6,prostaglandin E_(2),aspartate aminotransferase,alanine aminotransferase,total leucocyte count,and erythrocyte sedimentation rate while increasing IL-10 level.In addition,Cassia fistula extracts improved joint architecture,and prevented cartilage and bone destruction.Docking analysis demonstrated that the physcion,1-octacosanol,5,3’,4’-trihydroxy-6-methoxy-7-O-α-Lrhamnopyranosyl-(1,2)-O-β-D-galactopyranoside and scopoletin may be responsible for the anti-arthritic effect of Cassia fistula.Conclusions:Cassia fistula suppresses the progression of collagenⅡ-induced arthritis by lowering the inflammatory factors,decreasing paw volume and arthritic index,and alleviating joint architecture.However,further studies are required to confirm the bioactive molecule responsible for the anti-arthritic potential of Cassia fistula.展开更多
In this feeding trial rats were fed on diets of cereals from Kashin-Beck Disease (KBD) endemic area, Se-supplemented cereals from the above area, and cereals from Non-KBD endemic area. The purpose of this paper was to...In this feeding trial rats were fed on diets of cereals from Kashin-Beck Disease (KBD) endemic area, Se-supplemented cereals from the above area, and cereals from Non-KBD endemic area. The purpose of this paper was to investigate the effects of cereals from KBD endemic area and Se on the formation kinetics of cartilage type Ⅱ collagen fibril, the stability and ultrastructure of fibrils formed in vitro. The results indicated that low-selenium cereals from KBD endemic area resulted in a decelerated rate and extant of forming the type Ⅱ collagen fibril, the fibril stability reduced, fibril diameters diminished, and fibril banding periods increased or decreased in vitro. Sesupplemented cereals from KBD endemic area partially rectified the pathologic changes mentioned above. These data are important for further studying the etiology and pathology of KBD.展开更多
Damaged articular cartilage has very limited capacity for spontaneous healing. Tissue engineering provides a new hope for functional cartilage repair. Creation of an appropriate cell carrier is one of the critical ste...Damaged articular cartilage has very limited capacity for spontaneous healing. Tissue engineering provides a new hope for functional cartilage repair. Creation of an appropriate cell carrier is one of the critical steps for successful tissue engineering. With the supposition that a biomimetic construct might promise to generate better effects, we developed a novel composite scaffold and investigated its potential for cartilage tissue engineering.展开更多
Background Low back pain has emerged as a widespread disease often caused by intervertebral disc degeneration.This study aimed to establish an in vitro cell culture model of rhesus monkey lumbar intervertebral discs a...Background Low back pain has emerged as a widespread disease often caused by intervertebral disc degeneration.This study aimed to establish an in vitro cell culture model of rhesus monkey lumbar intervertebral discs and to investigate the effect of combined connective tissue growth factor （CTGF） and tissue inhibitor of metalloprotease-1（TIMP-1） expression mediated by adeno-associated virus （AAV） on collagen type Ⅱ and proteoglycan levels.The purpose of these investigations was to explore potential methods for relieving the degeneration of lumbar intervertebral disc cells.Methods Rhesus monkey lumbar intervertebral disc nucleus pulposus cells （NPCs） were isolated by enzyme digestion,cultured, and transduced with rAAV2-CTGF-IRES-TIMP-1, rAAV2-CTGF, or rAAV2-TIMP-1 at a multiplicity of infection （MOl） of 106.The expression of collagen type Ⅱ and proteoglycan was measured using RT-PCR and Western blotting.The synthetic rate of proteoglycan was measured using 35S incorporation.Results Rhesus monkey lumbar intervertebral disc NPCs were transduced with rAAV2-CTGF-IRES-TIMP-1,rAAV2-CTGF, and rAAV2-TIMP-1 and the transduced genes were expressed and detected.Compared to the control,CTGF promoted the synthesis of collagen type Ⅱ and proteoglycan.TIMP-1 showed an enhancing effect on the expression of proteoglycan but no effect on collagen type Ⅱ.Expression of both genes in rhesus monkey lumbar intervertebral disc NPCs significantly enhances the synthesis of proteoglycan and collagen type Ⅱ.Conclusions Single gene transduction of CTGF or TIMP-1 can enhanced synthesis of proteoglycan.CTGF expression can also enhance collagen type Ⅱ protein synthesis.Combined transduction of both CTGF and TIMP1 can significantly promote the expression of proteoglycan and collagen type Ⅱ to levels greater than transduction of a single gene alone.Our study provides a good basis for multi-gene therapy to treat lumbar intervertebral disc degeneration.展开更多
Objective：Although chondroprotective activities have been documented for polysaccharides,the potential target of different polysaccharide may differ.The study was aimed to explore the effect of glucan HBP-A in chondr...Objective：Although chondroprotective activities have been documented for polysaccharides,the potential target of different polysaccharide may differ.The study was aimed to explore the effect of glucan HBP-A in chondrocyte monolayer culture and chondrocytes-alginate hydrogel constructs in vivo,especially on the expression of type Ⅱ collagen.Methods：Chondrocytes isolated from rabbit articular cartilage were cultured and verified by immunocytochemical staining of type Ⅱ collagen.Chondrocyte viability was assessed after being treated with HBP-A in different concentrations.Morphological status of chondrocytes-alginate hydrogel constructs in vitro was observed by scanning electron microscope（SEM）.The constructs were treated with HBP-A and then injected to nude mice subcutaneously.Six weeks after transplantation,the specimens were observed through transmission electron microscopy（TEM）.The mRNA expressions of disintegrin and metalloproteinase with thrombospondin motifs 5（ADAMTs-5）,aggrecan and type Ⅱ collagen in both monolayer culture and constructs were determined by real time polymerase chain reaction（PCR）.The expression of typeⅡ collagen and matrix metalloproteinases-3（MMP-3） in chondrocyte monolayer culture was also tested through Western blot and enzyme linked immunosorbent assay（ELISA）,respectively.Results：MMP-3 secretion and ADAMTs-5 mRNA expression in vitro were inhibited by HBP-A at 0.3 mg/mL concentration.In morphological study,there were significant appearance of collagen in those constructs treated by HBP-A.Accordingly,in both chondrocyte monolayer culture and chondrocytes-alginate hydrogel constructs,the expression of type Ⅱcollagen was increased significantly in HBP-A group when compared with control group（P〈0.001）.Conclusions：The study documented that the potential pharmacological target of glucan HBP-A in chondrocytes monolayer culture and tissue engineered cartilage in vivo may be concerned with the inhibition of catabolic enzymes MMP-3,ADAMTs-5,and increasing of type Ⅱ collagen expression.展开更多
Background The most significant biological change in intervertebral disc degeneration is the decrease of chondrocyte specific gene and protein expression of Sox9 and collagen type Ⅱ. Interleukin-1 （IL-1） is not exp...Background The most significant biological change in intervertebral disc degeneration is the decrease of chondrocyte specific gene and protein expression of Sox9 and collagen type Ⅱ. Interleukin-1 （IL-1） is not expressed in the normal intervertebral disc tissue but increases in the degenerated intervertebral disc tissue. This suggests that IL-1 may play a role in regulation of the expression of Sox9 and collagen type Ⅱ. Methods Human intervertebral disc cells were isolated and cultured. Sox9 and collagen type Ⅱ expression during treatment with IL-1, with or without the nuclear factor-κB （NF-κB） activity inhibitor curcumin, were detected by using reverse transcription-polymerase chain reaction （RT-PCR） and Western blotting, and the activity of the NF-κB signaling pathway was detected by the electrophoretic mobility shift assay （EMSA）. Results IL-1 lowered the mRNA level and protein expression of Sox9 and collagen type Ⅱ in the cultured intervertebral disc cells in a dose dependent manner （P 〈0.05）, and this effect was attenuated by curcumin. Curcumin alone had no effect on Sox9 and collagen type Ⅱ expression （P 〉0.05）. IL-1 at concentrations of 0.1 ng/ml, 1 ng/ml and 10 ng/ml could stimulate the activity of NF-κB in the intervertebral disc cells in a dose dependent manner （P 〈0.05） that was inhibited by curcumin. Conclusions We demonstrated the previously unknown function of IL-1 in inhibiting Sox9 and collagen type Ⅱ via NF-κB in the intervertebral disc cells. This inhibition can be attenuated by curcumin, which is an effective NF-κB activity inhibitor.展开更多
To investigate the effects of oral administration of type Ⅱ collagen (CⅡ) on a djuvant arthritis (AA) in rats and its mechanisms, and to compare the effects of CⅡ with those of the Chinese traditional medicine Tri...To investigate the effects of oral administration of type Ⅱ collagen (CⅡ) on a djuvant arthritis (AA) in rats and its mechanisms, and to compare the effects of CⅡ with those of the Chinese traditional medicine Tripterygium Polyglycoside a dministered similarly Methods Arthritis was induced in rats by immunization using Freund's complete adjuvant ( FCA) After feeding rats either soluble CⅡ or Tripterygium Polyglycoside, chan ges in degree of articular swelling and articular histological findings were obs erved in AA rats Some correlative immunological indexes were measured, includi ng delayed type hypersensitivity (DTH) reaction, anti collagen and anti Mycoba cterium tuberculosis (MT) antibody in serum, and levels of IFN γ and TNF α i n articular steep in rats Results Oral administration of CⅡ was able to alleviate both distinctly articular and g eneral symptoms in AA rats, suppress synovium hyperplasia and inflammatory cells infiltration in arthrosis capsule The effects brought about by CⅡ were stron ger than those by Tripterygium Polyglycoside Oral administration of CⅡ inhibi ted antigen specific immune response, such as DTH and antibody reaction to CⅡ In addition, the expression of IFN γ and TNF α in joints were locally dow nregulated Conclusions The therapeutic effect of oral administration of CⅡ is obvious on adjuvant art hritis in rats Its remedial mechanisms are likely related to the downregulatio n of both IFN γ and TNF α, and the suppression of cell immunity展开更多
Background Repeated attacks of bronchial asthma lead to different degrees of airway remodeling,the mechanism of which is not yet clear. Some evidences indicate that it is related to the excessive expression of some gr...Background Repeated attacks of bronchial asthma lead to different degrees of airway remodeling,the mechanism of which is not yet clear. Some evidences indicate that it is related to the excessive expression of some growth promotion factors. Angiotensin Ⅱ is a polypeptide that may be involved in airway remodeling. To evaluate its role in airway remodeling in asthma,we observed the effects of an angiotensin Ⅱ type 1 receptor antagonist (valsartan) on the expression of collagen Ⅲ,collagen Ⅴ,and transforming growth factor β_1 (TGF-β_1) mRNA and protein in the airway walls of sensitized rats.Methods Forty Wistar rats were randomly divided into 5 groups: control group,sensitized group,and valsartan groups 1,2,and 3. The rats in the sensitized group and in valsartan groups 1,2,and 3 were sensitized and challenged with ovalbumin. Rats in control group were sensitized and challenged with 0.9% NaCl. Rats from valsartan groups 1,2,and 3 were drenched with valsartan (10 μg, 20 μg,or 30 μg,respectively) at the time of the ovalbumin challenges. The expression of collagen Ⅲ,collagen Ⅴ,and TGF-β_1 protein were detected using immunohistochemical method in combination with image analysis methods. The expression of TGF-β_1 mRNA was detected by in situ hybridization. Results The expression in the airways of collagen Ⅲ and collagen Ⅴ was significantly higher in rats from the sensitized group (7.73±0.81, 1.34±0.28) and from valsartan groups 1,2,and 3 (5.73±0.64, 1.13±0.15; 4.96±0.51, 0.98±0.08; 4.43±0.35, 0.93±0.06,respectively) than those in the control group (2.65±0.38, 0.67±0.08,P <0.05). In addition,collagen levels were significantly lower in valsartan groups 1,2,and 3 than those from the sensitized group ( P <0.05). The expression of TGF-β_1 mRNA and protein in the airways was significantly higher in rats from the sensitized group (20.49%±3.46%,29.73%±3.25%) and from valsartan groups 1,2,and 3 (16.47%±1.94%, 19.41%±1.87%; 14.38%±1.58%, 18.29%±1.43%; 12.96%±1.73%, 18.63%±1.11%,respectively) than that from the control group (7.84%±1.61%, 5.63%±1.07%,P <0.05). TGF-β_1 mRNA and protein levels were significantly lower in valsartan groups 1,2,and 3 than that in the sensitized group ( P <0.05). Conclusions Angiotensin Ⅱ receptor antagonist valsartan can suppress synthesis of collagen Ⅲ and collagen Ⅴ by downregulating TGF-β_1 mRNA and protein expression. Valsartan can decrease airway remodeling and could play a role in asthma therapy.展开更多
The resveratrol-enriched transgenic rice line Iksan526(IS526),first developed by the Rural Development Administration of Korea using genetic engineering techniques,shows beneficial health effects in mitigating metabol...The resveratrol-enriched transgenic rice line Iksan526(IS526),first developed by the Rural Development Administration of Korea using genetic engineering techniques,shows beneficial health effects in mitigating metabolic syndrome and obesity.However,the effects of IS526 on the differentiation of chondrocytes and the underlying mechanism have not been investigated in detail.In this study,the effects and cellular regulatory mechanisms of IS526 on rabbit articular chondrocytes were examined.Following IS526 callus extract treatment,the expression levels of differentiation-related proteins were detected via western blotting,Alcian blue staining and immune-luorescence staining.IS526 decreased the type Ⅱ collagen and proteoglycan levels in dose-and time-dependent manners.We further analyzed the effects of IS526 on skeleton genesis in zebrafish larvae using Alcian blue staining,which showed a reduction in cartilage formation along with increased production of matrix metalloproteinase(MMP)-13.IS526 also increased the phosphorylation of ERK1/2 and p38 kinase but inhibited the phosphorylation of Akt.Pharmacological inhibition of MMP-13 blocked the IS526-induced decrease in type Ⅱ collagen levels.Inhibition of p38 kinase or PI-3K/Akt with SB203580 and LY294002 enhanced the suppression of type Ⅱ collagen,but the blockage of ERK-1/2 by PD98059 rescued IS526-induced dedifferentiation.These results suggested that IS526 regulates type Ⅱ collagen and MMP-13 expression via the ERK1/2 and PI-3K/Akt pathways in rabbit articular chondrocytes.展开更多
基金supported by the Institute of Pharmaceutical Sciences,Kurukshetra University,Kurukshetra,Haryana,India,and Govt.College of Pharmacy,Rohru,District Shimla,Himachal Pradesh,India。
文摘Objective:To explore the effect of Cassia fistula on collagenⅡ-induced arthritis in rats.Methods:The effect of 250 and 500 mg/kg chloroform and hydroalcoholic extract of Cassia fistula leaf on collagenⅡ-induced arthritis was investigated by evaluating paw volume,arthritis index,spleen index,and biochemical parameters.Histopathological analysis and docking study were also performed.Results:A dose-dependent reduction in paw volume,arthritic index,and spleen index was observed following oral administration of the chloroform and hydroalcoholic extracts.Treatment with Cassia fistula extracts reduced tumor necrosis factor-α,interleukin(IL)-1β,IL-6,prostaglandin E_(2),aspartate aminotransferase,alanine aminotransferase,total leucocyte count,and erythrocyte sedimentation rate while increasing IL-10 level.In addition,Cassia fistula extracts improved joint architecture,and prevented cartilage and bone destruction.Docking analysis demonstrated that the physcion,1-octacosanol,5,3’,4’-trihydroxy-6-methoxy-7-O-α-Lrhamnopyranosyl-(1,2)-O-β-D-galactopyranoside and scopoletin may be responsible for the anti-arthritic effect of Cassia fistula.Conclusions:Cassia fistula suppresses the progression of collagenⅡ-induced arthritis by lowering the inflammatory factors,decreasing paw volume and arthritic index,and alleviating joint architecture.However,further studies are required to confirm the bioactive molecule responsible for the anti-arthritic potential of Cassia fistula.
文摘In this feeding trial rats were fed on diets of cereals from Kashin-Beck Disease (KBD) endemic area, Se-supplemented cereals from the above area, and cereals from Non-KBD endemic area. The purpose of this paper was to investigate the effects of cereals from KBD endemic area and Se on the formation kinetics of cartilage type Ⅱ collagen fibril, the stability and ultrastructure of fibrils formed in vitro. The results indicated that low-selenium cereals from KBD endemic area resulted in a decelerated rate and extant of forming the type Ⅱ collagen fibril, the fibril stability reduced, fibril diameters diminished, and fibril banding periods increased or decreased in vitro. Sesupplemented cereals from KBD endemic area partially rectified the pathologic changes mentioned above. These data are important for further studying the etiology and pathology of KBD.
基金This study was supported by a grant from Guangdong ProvincialScience &Technology Project, China (No. 2003A302102).
文摘Damaged articular cartilage has very limited capacity for spontaneous healing. Tissue engineering provides a new hope for functional cartilage repair. Creation of an appropriate cell carrier is one of the critical steps for successful tissue engineering. With the supposition that a biomimetic construct might promise to generate better effects, we developed a novel composite scaffold and investigated its potential for cartilage tissue engineering.
基金This study was supported by a grant from the National Natural Science Foundation of China （No. 30471750）.
文摘Background Low back pain has emerged as a widespread disease often caused by intervertebral disc degeneration.This study aimed to establish an in vitro cell culture model of rhesus monkey lumbar intervertebral discs and to investigate the effect of combined connective tissue growth factor （CTGF） and tissue inhibitor of metalloprotease-1（TIMP-1） expression mediated by adeno-associated virus （AAV） on collagen type Ⅱ and proteoglycan levels.The purpose of these investigations was to explore potential methods for relieving the degeneration of lumbar intervertebral disc cells.Methods Rhesus monkey lumbar intervertebral disc nucleus pulposus cells （NPCs） were isolated by enzyme digestion,cultured, and transduced with rAAV2-CTGF-IRES-TIMP-1, rAAV2-CTGF, or rAAV2-TIMP-1 at a multiplicity of infection （MOl） of 106.The expression of collagen type Ⅱ and proteoglycan was measured using RT-PCR and Western blotting.The synthetic rate of proteoglycan was measured using 35S incorporation.Results Rhesus monkey lumbar intervertebral disc NPCs were transduced with rAAV2-CTGF-IRES-TIMP-1,rAAV2-CTGF, and rAAV2-TIMP-1 and the transduced genes were expressed and detected.Compared to the control,CTGF promoted the synthesis of collagen type Ⅱ and proteoglycan.TIMP-1 showed an enhancing effect on the expression of proteoglycan but no effect on collagen type Ⅱ.Expression of both genes in rhesus monkey lumbar intervertebral disc NPCs significantly enhances the synthesis of proteoglycan and collagen type Ⅱ.Conclusions Single gene transduction of CTGF or TIMP-1 can enhanced synthesis of proteoglycan.CTGF expression can also enhance collagen type Ⅱ protein synthesis.Combined transduction of both CTGF and TIMP1 can significantly promote the expression of proteoglycan and collagen type Ⅱ to levels greater than transduction of a single gene alone.Our study provides a good basis for multi-gene therapy to treat lumbar intervertebral disc degeneration.
基金Supported by the National Natural Science Foundation of China(No.30300459,81072830)Shanghai Leading Academic Discipline Project(No.T0303)the Shanghai Youth Phospherus Project(No.08QA14063)
文摘Objective：Although chondroprotective activities have been documented for polysaccharides,the potential target of different polysaccharide may differ.The study was aimed to explore the effect of glucan HBP-A in chondrocyte monolayer culture and chondrocytes-alginate hydrogel constructs in vivo,especially on the expression of type Ⅱ collagen.Methods：Chondrocytes isolated from rabbit articular cartilage were cultured and verified by immunocytochemical staining of type Ⅱ collagen.Chondrocyte viability was assessed after being treated with HBP-A in different concentrations.Morphological status of chondrocytes-alginate hydrogel constructs in vitro was observed by scanning electron microscope（SEM）.The constructs were treated with HBP-A and then injected to nude mice subcutaneously.Six weeks after transplantation,the specimens were observed through transmission electron microscopy（TEM）.The mRNA expressions of disintegrin and metalloproteinase with thrombospondin motifs 5（ADAMTs-5）,aggrecan and type Ⅱ collagen in both monolayer culture and constructs were determined by real time polymerase chain reaction（PCR）.The expression of typeⅡ collagen and matrix metalloproteinases-3（MMP-3） in chondrocyte monolayer culture was also tested through Western blot and enzyme linked immunosorbent assay（ELISA）,respectively.Results：MMP-3 secretion and ADAMTs-5 mRNA expression in vitro were inhibited by HBP-A at 0.3 mg/mL concentration.In morphological study,there were significant appearance of collagen in those constructs treated by HBP-A.Accordingly,in both chondrocyte monolayer culture and chondrocytes-alginate hydrogel constructs,the expression of type Ⅱcollagen was increased significantly in HBP-A group when compared with control group（P〈0.001）.Conclusions：The study documented that the potential pharmacological target of glucan HBP-A in chondrocytes monolayer culture and tissue engineered cartilage in vivo may be concerned with the inhibition of catabolic enzymes MMP-3,ADAMTs-5,and increasing of type Ⅱ collagen expression.
基金The study was supported by a grant from the National Natural Science Foundation of China （No. 2004NSFC30471741）.
文摘Background The most significant biological change in intervertebral disc degeneration is the decrease of chondrocyte specific gene and protein expression of Sox9 and collagen type Ⅱ. Interleukin-1 （IL-1） is not expressed in the normal intervertebral disc tissue but increases in the degenerated intervertebral disc tissue. This suggests that IL-1 may play a role in regulation of the expression of Sox9 and collagen type Ⅱ. Methods Human intervertebral disc cells were isolated and cultured. Sox9 and collagen type Ⅱ expression during treatment with IL-1, with or without the nuclear factor-κB （NF-κB） activity inhibitor curcumin, were detected by using reverse transcription-polymerase chain reaction （RT-PCR） and Western blotting, and the activity of the NF-κB signaling pathway was detected by the electrophoretic mobility shift assay （EMSA）. Results IL-1 lowered the mRNA level and protein expression of Sox9 and collagen type Ⅱ in the cultured intervertebral disc cells in a dose dependent manner （P 〈0.05）, and this effect was attenuated by curcumin. Curcumin alone had no effect on Sox9 and collagen type Ⅱ expression （P 〉0.05）. IL-1 at concentrations of 0.1 ng/ml, 1 ng/ml and 10 ng/ml could stimulate the activity of NF-κB in the intervertebral disc cells in a dose dependent manner （P 〈0.05） that was inhibited by curcumin. Conclusions We demonstrated the previously unknown function of IL-1 in inhibiting Sox9 and collagen type Ⅱ via NF-κB in the intervertebral disc cells. This inhibition can be attenuated by curcumin, which is an effective NF-κB activity inhibitor.
文摘To investigate the effects of oral administration of type Ⅱ collagen (CⅡ) on a djuvant arthritis (AA) in rats and its mechanisms, and to compare the effects of CⅡ with those of the Chinese traditional medicine Tripterygium Polyglycoside a dministered similarly Methods Arthritis was induced in rats by immunization using Freund's complete adjuvant ( FCA) After feeding rats either soluble CⅡ or Tripterygium Polyglycoside, chan ges in degree of articular swelling and articular histological findings were obs erved in AA rats Some correlative immunological indexes were measured, includi ng delayed type hypersensitivity (DTH) reaction, anti collagen and anti Mycoba cterium tuberculosis (MT) antibody in serum, and levels of IFN γ and TNF α i n articular steep in rats Results Oral administration of CⅡ was able to alleviate both distinctly articular and g eneral symptoms in AA rats, suppress synovium hyperplasia and inflammatory cells infiltration in arthrosis capsule The effects brought about by CⅡ were stron ger than those by Tripterygium Polyglycoside Oral administration of CⅡ inhibi ted antigen specific immune response, such as DTH and antibody reaction to CⅡ In addition, the expression of IFN γ and TNF α in joints were locally dow nregulated Conclusions The therapeutic effect of oral administration of CⅡ is obvious on adjuvant art hritis in rats Its remedial mechanisms are likely related to the downregulatio n of both IFN γ and TNF α, and the suppression of cell immunity
基金ThisworkwassupportedbyagrantfromtheShanxiProvinceFoundationforReturnedOverseasChineseScholars (No 9913 -95 )
文摘Background Repeated attacks of bronchial asthma lead to different degrees of airway remodeling,the mechanism of which is not yet clear. Some evidences indicate that it is related to the excessive expression of some growth promotion factors. Angiotensin Ⅱ is a polypeptide that may be involved in airway remodeling. To evaluate its role in airway remodeling in asthma,we observed the effects of an angiotensin Ⅱ type 1 receptor antagonist (valsartan) on the expression of collagen Ⅲ,collagen Ⅴ,and transforming growth factor β_1 (TGF-β_1) mRNA and protein in the airway walls of sensitized rats.Methods Forty Wistar rats were randomly divided into 5 groups: control group,sensitized group,and valsartan groups 1,2,and 3. The rats in the sensitized group and in valsartan groups 1,2,and 3 were sensitized and challenged with ovalbumin. Rats in control group were sensitized and challenged with 0.9% NaCl. Rats from valsartan groups 1,2,and 3 were drenched with valsartan (10 μg, 20 μg,or 30 μg,respectively) at the time of the ovalbumin challenges. The expression of collagen Ⅲ,collagen Ⅴ,and TGF-β_1 protein were detected using immunohistochemical method in combination with image analysis methods. The expression of TGF-β_1 mRNA was detected by in situ hybridization. Results The expression in the airways of collagen Ⅲ and collagen Ⅴ was significantly higher in rats from the sensitized group (7.73±0.81, 1.34±0.28) and from valsartan groups 1,2,and 3 (5.73±0.64, 1.13±0.15; 4.96±0.51, 0.98±0.08; 4.43±0.35, 0.93±0.06,respectively) than those in the control group (2.65±0.38, 0.67±0.08,P <0.05). In addition,collagen levels were significantly lower in valsartan groups 1,2,and 3 than those from the sensitized group ( P <0.05). The expression of TGF-β_1 mRNA and protein in the airways was significantly higher in rats from the sensitized group (20.49%±3.46%,29.73%±3.25%) and from valsartan groups 1,2,and 3 (16.47%±1.94%, 19.41%±1.87%; 14.38%±1.58%, 18.29%±1.43%; 12.96%±1.73%, 18.63%±1.11%,respectively) than that from the control group (7.84%±1.61%, 5.63%±1.07%,P <0.05). TGF-β_1 mRNA and protein levels were significantly lower in valsartan groups 1,2,and 3 than that in the sensitized group ( P <0.05). Conclusions Angiotensin Ⅱ receptor antagonist valsartan can suppress synthesis of collagen Ⅲ and collagen Ⅴ by downregulating TGF-β_1 mRNA and protein expression. Valsartan can decrease airway remodeling and could play a role in asthma therapy.
基金This work was supported by the National Research Foundation of Korea funded by the Korean Government(Grant No.2017R1D1A3B03033401)the Center for Women in Science,Engineering and Technology Grant funded by the Ministry of Science and ICT under the Program for Returners into Research and Development.
文摘The resveratrol-enriched transgenic rice line Iksan526(IS526),first developed by the Rural Development Administration of Korea using genetic engineering techniques,shows beneficial health effects in mitigating metabolic syndrome and obesity.However,the effects of IS526 on the differentiation of chondrocytes and the underlying mechanism have not been investigated in detail.In this study,the effects and cellular regulatory mechanisms of IS526 on rabbit articular chondrocytes were examined.Following IS526 callus extract treatment,the expression levels of differentiation-related proteins were detected via western blotting,Alcian blue staining and immune-luorescence staining.IS526 decreased the type Ⅱ collagen and proteoglycan levels in dose-and time-dependent manners.We further analyzed the effects of IS526 on skeleton genesis in zebrafish larvae using Alcian blue staining,which showed a reduction in cartilage formation along with increased production of matrix metalloproteinase(MMP)-13.IS526 also increased the phosphorylation of ERK1/2 and p38 kinase but inhibited the phosphorylation of Akt.Pharmacological inhibition of MMP-13 blocked the IS526-induced decrease in type Ⅱ collagen levels.Inhibition of p38 kinase or PI-3K/Akt with SB203580 and LY294002 enhanced the suppression of type Ⅱ collagen,but the blockage of ERK-1/2 by PD98059 rescued IS526-induced dedifferentiation.These results suggested that IS526 regulates type Ⅱ collagen and MMP-13 expression via the ERK1/2 and PI-3K/Akt pathways in rabbit articular chondrocytes.
