Upregulation of pleiotrophin expression in rat hepatic stellate cells by PDGF and hypoxia: Implications for its role in experimental biliary liver fibrogenesis
Upregulation of pleiotrophin expression in rat hepatic stellate cells by PDGF and hypoxia: Implications for its role in experimental biliary liver fibrogenesis
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DOI：
10.1016/j.bbrc.2005.09.173
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发表时间：
2005-12-02
影响因子：
3.1
通讯作者：
Kiefer, P
中科院分区：
文献类型：
--
作者：
Antoine, M;Tag, CG;Kiefer, P
多效生长因子（Pleiotrophin，PTN）是一种分泌型肝素结合蛋白，具有多种生物学活性，包括促有丝分裂、促血管生成等。和损伤后的组织修复。最近的研究表明，PTN是肝细胞的强有丝分裂原，并参与肝再生。在成年肝细胞中，Ptn基因主要表达于静止期肝星状细胞（HSC）。虽然我们已经能够证明间变性淋巴瘤激酶的mRNA和蛋白质表达的受体酪氨酸激酶的PTN的HSC，PTN没有作为一个有丝分裂原的HSC相比，肝细胞。PTN免疫反应性显着增加实验性肝纤维化胆总管结扎和观察窦HSC。在原代HSC培养物中，PDGF-BB显著增加Ptn转录。在低氧环境下。从机制上讲，缺氧和PDGF介导的诱导PTN在肝窦HSC中的表达可以为肝细胞提供强的促有丝分裂信号，以限制胆源性肝纤维化中对实质细胞的损伤。(c)2005年爱思唯尔公司All rights reserved.
Pleiotrophin (PTN) is a secretory heparin binding protein with various biological activities including mitogenesis, angiogenesis. and tissue repair after injury. Recent Studies have shown that PTN is a strong mitogen of hepatocytes and involved in liver regeneration. In adult liver cells Ptn gene is mainly expressed by quiescent hepatic stellate cells (HSCs). Although we have been able to demonstrate mRNA and protein expression of the anaplastic lymphoma kinase-the receptor tyrosine kinase for PTN-on HSCs, PTN did not act as a mitogen of HSCs in contrast to hepatocytes. PTN immunoreactivity was markedly increased in experimental fibrogenesis by common bile duct ligation and observed in sinusoidal HSCs. In primary HSC Cultures, Ptn transcription was significantly increased by PDGF-BB. and under hypoxic atmosphere. Mechanistically, hypoxia and PDGF mediated induction of PTN expression in sinusoidal HSCs may provide a strong mitogenic signal for hepatocytes to limit the damage to the parenchymal cells in biliary-type liver fibrogenesis. (c) 2005 Elsevier Inc. All rights reserved.