论文部分内容阅读
AIM:To study the expression of cystatin C(CysC),itsregulation by transforming growth factor-β1(TGF-β1)and platelet-derived growth factor(PDGF)and thepotential interference of CysC with TGF-β1 signaling inthis special celt type.METHODS:We evaluated the CysC expression incultured,profibrogenic hepatic stellate cells and trans-differentiated myofibroblasts by Northern and Westernblotting and confocal laser scanning microscopy.RESULTS:CysC was increased significantly in thecourse of trans-differentiation.Both TGF-β1 and PDGF-BB suppressed CysC expression.Furthermore,CysCsecretion was induced by the treatment with TGF-β1.Although CysC induced an increased binding affinityof TGF-β receptor type Ⅲ(beta-glycan)as assessedby chemical cross-linking with [~(125)Ⅰ]-TGF-β1,it did notmodulate TGF-β1 signal transduction as shown byevaluating the Smad2/3 phosphorylation status and[CAGA]-MLP-luciferase reporter gene assay.Interestingly,the shedding of type III TGF-β receptor beta-glycanwas reduced in CysC-treated cells.Our data indicatedthat CysC expression was upregulated during trans-differentiation.CONCLUSION:Increased CysC levels in the serum ofpatients suffering from liver diseases are at least partiallydue to a higher expression in activated hepatic stellatecells.Furthermore,TGF-β1 influences the secretion ofCysC,highlighting a potentially important role of cysteineproteases in the progression of hepatic fibrogenesis.
AIM: To study the expression of cystatin C (CysC), its regulation by transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) and the potential interference of CysC with TGF-β1 signaling in special celt type. METHODS : We evaluated the CysC expression in cultured, profibrogenic hepatic stellate cells and trans-differentiated myofibroblasts by Northern and Western blotting and confocal laser scanning microscopy. RESULTS: CysC was increased significantly in theourse of trans-differentiation. Both TGF-β1 and PDGF-BB suppressed CysC Expression.Furthermore, CysCrecretion was induced by the treatment with TGF-β1. CysC induced an increased binding affinityof TGF-β receptor type Ⅲ (beta-glycan) as assessed by chemical cross-linking with [~ (125) I] β1, it did not modulate TGF-β1 signal transduction as shown by evaluating the Smad2 / 3 phosphorylation status and [CAGA] -MLP-luciferase reporter gene assay. Interestingly, the shedding of type III TGF-β receptor beta-glycanwas reduced in CysC-treated cells. Our data indicated that upregulated during trans-differentiation. CONCLUSION: Increased CysC levels in the serum of patients suffering from liver diseases are at least partially up to a higher expression in activated hepatic stellate cells. influences the secretion ofCysC, highlighting a potentially important role of cysteineproteases in the progression of hepatic fibrogenesis.