Effects of lysophosphatidic acid on proliferation of stellate cells and hepatocytes in culture
Effects of lysophosphatidic acid on proliferation of stellate cells and hepatocytes in culture
复制标题
DOI：
10.1006/bbrc.1998.8983
复制
发表时间：
1998-07-20
影响因子：
3.1
通讯作者：
Fujiwara, K
中科院分区：
文献类型：
--
作者：
Ikeda, H;Yatomi, Y;Fujiwara, K
溶血磷脂酸（LPA）是由活化的血小板产生和释放的成纤维细胞或平滑肌细胞的生长因子样介质。血小板活化发生在肝坏死和随后的肝再生和纤维化。在肝纤维化过程中，肝星状细胞增殖并向肌成纤维细胞转化。因此，本实验研究了LPA对肝细胞和星状细胞增殖的影响。在培养的大鼠星状细胞中，LPA增加DNA合成，增强MAP激酶活性。百日咳毒素（PTX）减弱了这种促有丝分裂作用。与此相反，LPA降低肝细胞生长因子（HGF）或表皮生长因子（EGF）诱导的培养大鼠肝细胞的DNA合成，而不影响蛋白质合成。HGF或EGF增强的MAP激酶活性不受LPA的影响。PTX可减弱这种抗有丝分裂的作用，培养基中TGF β水平低于LPA抑制DNA合成的有效水平。结果提示，LPA可能影响伴有血小板活化的肝病肝细胞和星状细胞的增殖。(C)北京：科学出版社.
Lysophosphatidic acid (LPA) is a growth factor-like mediator for fibroblasts or smooth muscle cells produced and released by activated platelets. Platelet activation occurs with hepatic necrosis and subsequent liver regeneration and fibrosis. In the fibrosis, hepatic stellate cells proliferate with phenotypic transformation to myofibroblasts, Thus, effects of LPA on proliferation of hepatocytes and stellate cells were investigated. In cultured rat stellate cells, LPA increased DNA synthesis with enhanced MAP kinase activity. Pertussis toxin (PTX) attenuated this mitogenic action. In contrast, LPA decreased DNA synthesis by cultured rat hepatocytes induced by hepatocyte growth factor (HGF) or epidermal growth factor (EGF) without affecting protein synthesis. Enhanced MAP kinase activity by HGF or EGF was not changed by LPA. This anti-mitogenic action was attenuated by PTX TGF beta level in the medium was less than the level effective for inhibiting the DNA synthesis in the presence of LPA Our results suggest that LPA might affect proliferation of hepatocytes and stellate cells in liver diseases complicating platelet activation. (C) 1998 Academic Press.