AIM: To explore different roles of TGF-β (transforming growth factor beta) and bone morphogenetic proteins (BMPs)in hepatic stellate cell proliferation and trans-differentiation.METHODS: Hepatic stellate cells were i...AIM: To explore different roles of TGF-β (transforming growth factor beta) and bone morphogenetic proteins (BMPs)in hepatic stellate cell proliferation and trans-differentiation.METHODS: Hepatic stellate cells were isolated from male Sprague-Dawley rats. Sub-cultured hepatic stellate cells were employed for cell proliferation assay with WST-1 reagent and Western blot analysis with antibody against smooth muscle alpha actin (SMA).RESULTS: The results indicated that TGF-β1 significantly inhibited cell proliferation at concentration as low as 0.1 ng/ml, but both BMP-2 and BMP-4 did not affect cell proliferation at concentration as high as 10 ng/ml. The effect on hepatic stellate cell trans-differentiation was similar between TGFβ1 and BMPs. However, BMPs was more potent at transdifferentiation of hepatic stellate cells than TGF-β1. In addition, we observed that TGF-β1 transient reduced the abundance of SMA in hepatic stellate cells.CONCLUSION: TGF-β may be more important in regulation of hepatic stellate cell proliferation while BMPs may be the major cytokines regulating hepatic stellate cell transdifferentiation.展开更多
AIM： To study the effect of rosiglitazone, which is a ligand of peroxisome proliferator-activated receptor gamma （PPARy）, on the expression of PPARy in hepatic stellate cells （HSCs） and on the biological characte...AIM： To study the effect of rosiglitazone, which is a ligand of peroxisome proliferator-activated receptor gamma （PPARy）, on the expression of PPARy in hepatic stellate cells （HSCs） and on the biological characteristics of HSCs. METHODS： The activated HSCs were divided into three groups： control group, 3 μmol/L rosiglitazone group, and 10 μmol/L rosiglitazone group. The expression of PPARγ, α-smooth muscle actin （α-SMA）, and type Ⅰ and Ⅲ collagen was detected by RT-PCR, Western blot and immunocytochemical staining, respectively. Cell proliferation was determined with methylthiazolyltetrazolium （MTT） colodmetric assay. Cell apoptosis was demonstrated with flow cytometry. RESULTS： The expression of PPARγ at mRNA and protein level markedly increased in HSCs of 10 μmol/L rosiglitazone group （tvalue was 10.870 and 4.627 respectively, P〈0.01 in both）. The proliferation of HSCs in 10 μmol/L rosiglitazone group decreased significantly （t = 5.542, P〈0.01）, α-SMA expression level and type Ⅰ collagen synthesis ability were also reduced VS controls （tvalue = 10.256 and 14.627 respectively, P〈0.01 in both）. The apoptotic rate of HSCs significantly increased in 10 μmol/L rosiglitazone group vs control （X^2= 16.682, P〈0.01）. CONCLUSION： By increasing expression of PPARγ in activated HSCs, rosiglitazone, an agonist of PPARγ, decreases α-SNA expression and type Ⅰ collagen synthesis, inhibits cell proliferation, and induces cell apoptosis.展开更多
文摘AIM: To explore different roles of TGF-β (transforming growth factor beta) and bone morphogenetic proteins (BMPs)in hepatic stellate cell proliferation and trans-differentiation.METHODS: Hepatic stellate cells were isolated from male Sprague-Dawley rats. Sub-cultured hepatic stellate cells were employed for cell proliferation assay with WST-1 reagent and Western blot analysis with antibody against smooth muscle alpha actin (SMA).RESULTS: The results indicated that TGF-β1 significantly inhibited cell proliferation at concentration as low as 0.1 ng/ml, but both BMP-2 and BMP-4 did not affect cell proliferation at concentration as high as 10 ng/ml. The effect on hepatic stellate cell trans-differentiation was similar between TGFβ1 and BMPs. However, BMPs was more potent at transdifferentiation of hepatic stellate cells than TGF-β1. In addition, we observed that TGF-β1 transient reduced the abundance of SMA in hepatic stellate cells.CONCLUSION: TGF-β may be more important in regulation of hepatic stellate cell proliferation while BMPs may be the major cytokines regulating hepatic stellate cell transdifferentiation.
基金Supported by the National Natural Science Foundation of China,No. 30371387
文摘AIM： To study the effect of rosiglitazone, which is a ligand of peroxisome proliferator-activated receptor gamma （PPARy）, on the expression of PPARy in hepatic stellate cells （HSCs） and on the biological characteristics of HSCs. METHODS： The activated HSCs were divided into three groups： control group, 3 μmol/L rosiglitazone group, and 10 μmol/L rosiglitazone group. The expression of PPARγ, α-smooth muscle actin （α-SMA）, and type Ⅰ and Ⅲ collagen was detected by RT-PCR, Western blot and immunocytochemical staining, respectively. Cell proliferation was determined with methylthiazolyltetrazolium （MTT） colodmetric assay. Cell apoptosis was demonstrated with flow cytometry. RESULTS： The expression of PPARγ at mRNA and protein level markedly increased in HSCs of 10 μmol/L rosiglitazone group （tvalue was 10.870 and 4.627 respectively, P〈0.01 in both）. The proliferation of HSCs in 10 μmol/L rosiglitazone group decreased significantly （t = 5.542, P〈0.01）, α-SMA expression level and type Ⅰ collagen synthesis ability were also reduced VS controls （tvalue = 10.256 and 14.627 respectively, P〈0.01 in both）. The apoptotic rate of HSCs significantly increased in 10 μmol/L rosiglitazone group vs control （X^2= 16.682, P〈0.01）. CONCLUSION： By increasing expression of PPARγ in activated HSCs, rosiglitazone, an agonist of PPARγ, decreases α-SNA expression and type Ⅰ collagen synthesis, inhibits cell proliferation, and induces cell apoptosis.
