摘要
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 this special cell type. METHODS： We evaluated the CysC expression in cultured, profibrogenic hepatic stellate cells and transdifferentiated myofibroblasts by Northern and Western blotting and confocal laser scanning microscopy. RESULTS： CysC was increased significantly in the course of trans-differentiation. Both TGF-β1 and PDGFBB suppressed CysC expression. Furthermore, CysC secretion was induced by the treatment with TGF-β1. Although CysC induced an increased binding affinity of TGF-β receptor type Ⅲ （beta-glycan） as assessed by chemical cross-linking with [^125I]-TGF-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-glycan was reduced in CysC-treated cells. Our data indicated that CysC expression was upregulated during transdifferentiation. CONCLUSION： Increased CysC levels in the serum of patients suffering from liver diseases are at least partially due to a higher expression in activated hepatic stellate cells. Furthermore, TGF-β1 influences the secretion of CysC, highlighting a potentially important role of cysteine proteases in the progression of hepatic fibrogenesis.
瞄准：学习 C (CysC ) ，它由转变生长 factor-beta1 (TGF-beta1 ) 的规定和导出血小板的生长因素(PDGF ) 和有在这个特殊房间发信号的 TGF-beta1 的 CysC 的潜在的干扰打的 cystatin 的表示。方法：我们计算了 CysC 表达式在有教养， profibrogenic 肝的星形细胞和区分 trans 的 myofibroblasts 由北、西方弄污并且共焦的激光扫描显微镜学。结果：CysC 在 trans 区别期间显著地被增加。TGF-beta1 和 PDGF-BB 压制了 CysC 表示。而且， CysC 分泌物被处理与 TGF-beta1 导致。尽管 CysC 导致了 TGF 贝它的一种增加的有约束力的亲密关系，受体是由化学 cross-linking 估计了与打 III (beta-glycan )[125I ] 它没调制的 -TGF-beta1, 由评估 Smad2/3 磷酸化地位出现的 TGF-beta1 信号转导变异并且[CAGA ]-MLP-luciferase 记者基因试金。有趣地，流类型 III TGF 贝它受体 beta-glycan 在对待 CysC 的房间被减少。我们的数据显示那 CysC 表情起来在 trans 区别期间调整了。结论：在患肝疾病的病人的浆液的增加的 CysC 层次是至少部分由于在激活的肝的星形细胞的更高的表情。而且， TGF-beta1 影响 CysC 的分泌物，加亮在肝的纤维发生的前进的半胱氨酸朊酶的一个潜在地重要的角色。
基金
Supported by the Federal Ministry of Education
Research of Germany(Network of Excellence in Viral Hepatitis Hep-Net)and the Deutsche Forschungsgemeinschaft(SFB-6542,TPA9)to RW and AMG
