Expression of activin A is increased in cirrhotic and fibrotic rat livers
Expression of activin A is increased in cirrhotic and fibrotic rat livers
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DOI：
10.1016/s0016-5085(98)70539-6
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发表时间：
1998-03-01
期刊：
影响因子：
29.4
通讯作者：
Asakura, H
中科院分区：
文献类型：
--
作者：
Sugiyama, M;Ichida, T;Asakura, H
背景和目标：活化素A是转化生长因子β（transforming growth factor，TGF β）超家族的成员，近年来研究发现，活化素A可抑制肝细胞DNA合成，诱导肝细胞凋亡。这些生物学功能与肝硬化中过度表达的TGF-β 1相似。本研究的目的是检查激活素A是否参与肝硬化和纤维化。方法：采用二甲基亚硝胺或猪血清腹腔注射诱导大鼠肝硬化或肝纤维化模型。用北方印迹法检测活化素A在肝硬化、肝纤维化和原代培养大鼠肝细胞中mRNA表达的动力学变化，并用免疫组化法检测活化素A的定位。1型胶原mRNA表达的激活素A在大鼠培养的伊藤/脂肪储存细胞和成纤维细胞的调制也进行了检查。结果：北方印迹法显示肝纤维化大鼠肝组织中激活素A mRNA表达增强。表达免疫活性素A的肝细胞数量显著增加，尤其是在纤维化区域周围。TGF-β 1和激活素A本身可显著增加培养肝细胞中激活素A mRNA的表达。此外，激活素A和TGF-β 1以协同方式增强培养细胞中的1型胶原mRNA表达。结论：激活素A在大鼠肝硬化和肝纤维化中过度表达，可能参与肝纤维化的发生。
Background & Aims: Activin A, a member of the transforming growth factor (TGF)-beta superfamily, recently has been reported to suppress DNA synthesis and to induce apoptosis of hepatocytes. These biological functions are similar to those of TGF-beta 1, which is overexpressed in liver cirrhosis. The aim of this study was to examine whether activin A is involved in liver cirrhosis and fibrosis. Methods: Liver cirrhosis or fibrosis was induced by intraperitoneal injections of dimethylnitrosamine or porcine serum into rats. The kinetics of activin A messenger RNA (mRNA) expression in cirrhotic and fibrotic livers and primary cultured rat hepatocytes were assessed by Northern blotting, and the localization of activin A was determined immunohistochemically. Modulation of type 1 collagen mRNA expression by activin A in rat cultured Ito/fat-storing cells and fibroblasts was also examined. Results: Northern blotting showed that activin A mRNA expression was enhanced in fibrotic livers. The numbers of hepatocytes expressing immunoreactive activin A were significantly greater, especially around the fibrotic areas. Activin A mRNA expression in cultured hepatocytes was increased significantly by TGF-beta 1 and by activin A itself. Furthermore, type 1 collagen mRNA expression in cultured cells was enhanced by activin A and TGF-beta 1 in a synergistic manner. Conclusions: Activin A is overexpressed in rat cirrhotic and fibrotic livers and may contribute to hepatic fibrogenesis.