Differential regulation of activin A for hepatocyte growth and fibronectin synthesis in rat liver injury

被引:73
作者
Date, M [1 ]
Matsuzaki, K [1 ]
Matsushita, M [1 ]
Tahashi, Y [1 ]
Sakitani, K [1 ]
Inoue, K [1 ]
机构
[1] Kansai Med Univ, Dept Internal Med 3, Moriguchi, Osaka 5708506, Japan
关键词
activin receptor; extracellular matrix; fibronectin; liver regeneration; TGF-beta;
D O I
10.1016/S0168-8278(00)80070-7
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background/Aims: Both hepatocyte growth and production of extracellular matrix such as fibronectin are essential for liver regeneration. Although activin A is reported to inhibit DNA replication in rat hepatocytes, the role of activin A for liver regeneration after acute injury has not been fully assessed. This study investigated the mechanism by which hepatocyte growth is regulated by activin A during liver regeneration and the effects of activin A on extracellular matrix production. Methods: The mRNA for PA subunit of activin A and activin receptors in hepatocytes and hepatic stellate cells after CCl4 administration were studied by Northern blotting, Binding of I-125-activin A was tested in these cells, Effects of activin A were examined by DNA, collagen and fibronectin synthesis. Results: PA mRNA was expressed in quiescent hepatocytes, and this expression peaked 12 h after CCl4 administration. Activin receptor mRNAs and cross-linked ligand/receptor complexes were expressed in hepatocytes and hepatic stellate cells. However, these levels decreased specifically in hepatocytes at 24 h and had normalized by 72 h. The down-regulation of activin receptor was also observed after partial hepatectomy. Antiproliferative response to activin A decreased in hepatocytes at 24 h, Activin A stimulated production of fibronectin by hepatic stellate cells, but the synthesis of collagen was only slightly elevated in hepatic stellate cells following activin stimulation. Conclusions: The down-regulation of activin receptors in hepatocytes may be partly responsible for these cells becoming responsive to mitogenic stimuli, The increase of activin A at the early stage of liver injury has the potential to contribute to the regulation of fibronectin production in hepatic stellate cells.
引用
收藏
页码:251 / 260
页数:10
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