AIM:The transforming growth factor-beta(TGF-β)/Smad signaling pathway system plays a prominent role in the control of cell growth and extracellular matrix formation in the progression of liver fibrogenesis.Smad prote...AIM:The transforming growth factor-beta(TGF-β)/Smad signaling pathway system plays a prominent role in the control of cell growth and extracellular matrix formation in the progression of liver fibrogenesis.Smad proteins can either positively or negatively regulate TGF-βresponses.In this study,the therapeutic effects of Chinese traditional compound decoction,JinSanE,and the changes of TGF-β/Smad signaling pathway system in carbon tetrachloride(CCl4)-induced rat experimental liver fibrosis were examined.METHODS:Seventy-two healthy Wistar rats were assigned to groups including normal control group,CCl4 model group,JinSanE treatment group I and JinSanE treatment group II.Each group contained 18 rats.All groups,except the normal control group,received CCl4 subcutaneous injection for 8 wk.Rats in JinSanE groups I and II were orally treated with JinSanE daily at the 1st and 5th wk,respectively,after exposure to CCl4.The expression of TGF-β1 and TGF-β1 type II receptor(TRII)mRNA in the liver was determined by reverse transcription polymerase chain reaction,and the expression of TGF-β1,Smad3 and Smad7 by immunohistochemistry.The liver histopathology was also examined by HE staining and observed under electron microscope.The activities of several serum fibrosis-associated enzymes,alanine aminotransferase(ALT),aspartate aminotransferase(AST),the levels of serum hyaluronic acid(HA)were assayed.RESULTS:Hepatic fibrosis caused by CCl4 was significantly inhibited in the JinSanE-treated groups.The degrees of necrosis/degeneration and fibrosis scores were significantly lower in the JinSanE-treated groups than in the model control group.The expression of TGF-β1,TRII and Smad3 was significantly higher in the model group than that in the JinSanE-treated groups,and the active/total TGF-β1 ratio in the JinSanE groups was suppressed.Expression of TRII mRNA and Smad3 proteins snowed a distribution pattern similar to that of TGF-β1 with a direct correlation in terms of the degree of hepatic fibrosis.The amount of positive staining Smad7 cells was significantly less in the model group than in the JinSanE-treated groups and the normal group.The contents of ALT,AST and HA were significantly lower in the JinSanE-treated groups than those in the model group.CONCLUSION:Traditional Chinese medicine,JinSanE,prevents the progression of hepatic damage and fibrosis through the inhibition of TGF-β1,TRII and Smad3 signal proteins,and increases expression of Smad7 signal protein in vivo.展开更多
基金Supported by the Basic Research Program of Hubei Province Education Bureau,No.2003X113.
文摘AIM:The transforming growth factor-beta(TGF-β)/Smad signaling pathway system plays a prominent role in the control of cell growth and extracellular matrix formation in the progression of liver fibrogenesis.Smad proteins can either positively or negatively regulate TGF-βresponses.In this study,the therapeutic effects of Chinese traditional compound decoction,JinSanE,and the changes of TGF-β/Smad signaling pathway system in carbon tetrachloride(CCl4)-induced rat experimental liver fibrosis were examined.METHODS:Seventy-two healthy Wistar rats were assigned to groups including normal control group,CCl4 model group,JinSanE treatment group I and JinSanE treatment group II.Each group contained 18 rats.All groups,except the normal control group,received CCl4 subcutaneous injection for 8 wk.Rats in JinSanE groups I and II were orally treated with JinSanE daily at the 1st and 5th wk,respectively,after exposure to CCl4.The expression of TGF-β1 and TGF-β1 type II receptor(TRII)mRNA in the liver was determined by reverse transcription polymerase chain reaction,and the expression of TGF-β1,Smad3 and Smad7 by immunohistochemistry.The liver histopathology was also examined by HE staining and observed under electron microscope.The activities of several serum fibrosis-associated enzymes,alanine aminotransferase(ALT),aspartate aminotransferase(AST),the levels of serum hyaluronic acid(HA)were assayed.RESULTS:Hepatic fibrosis caused by CCl4 was significantly inhibited in the JinSanE-treated groups.The degrees of necrosis/degeneration and fibrosis scores were significantly lower in the JinSanE-treated groups than in the model control group.The expression of TGF-β1,TRII and Smad3 was significantly higher in the model group than that in the JinSanE-treated groups,and the active/total TGF-β1 ratio in the JinSanE groups was suppressed.Expression of TRII mRNA and Smad3 proteins snowed a distribution pattern similar to that of TGF-β1 with a direct correlation in terms of the degree of hepatic fibrosis.The amount of positive staining Smad7 cells was significantly less in the model group than in the JinSanE-treated groups and the normal group.The contents of ALT,AST and HA were significantly lower in the JinSanE-treated groups than those in the model group.CONCLUSION:Traditional Chinese medicine,JinSanE,prevents the progression of hepatic damage and fibrosis through the inhibition of TGF-β1,TRII and Smad3 signal proteins,and increases expression of Smad7 signal protein in vivo.
