- 作者: Pisit Tangkijvanich Andrew C. Melton Chintda Santiskulvong Hal F. Yee Jr.
- 作者服務機構: Departments of Medicine and Physiology, and CURE Digestive Diseases Research Center, David Geffen School of Medicine at UCLA, Los Angeles, Calif., USA
- 中文摘要: --
- 英文摘要: Although hepatic myofibroblast migration plays a keyrole in the liver's injury response, the signal transductionpathways mediating the migration of this cell type areuncertain. Recently, we reported that lysophosphatidicacid (LPA) stimulates the migration of hepatic myofibro-blasts. The goal of this study was to test the hypothesisthat rho and p38 MAP kinase signaling pathways me-diate LPA-stimulated hepatic myofibroblast migration.We measured migration, myosin regulatory light chainand p38 MAP kinase phosphorylation, and contractileforce generation by human hepatic myofibroblasts. LPAstimulated migration in a dose-dependent and saturablemanner that was partially blocked by Y-27632, a rho-associated kinase inhibitor, as well as by SB-202190, ap38 MAP kinase inhibitor. LPA also induced myosin reg-ulatory light chain phosphorylation and contractile forcegeneration in a Y-27632 dependent, and SB-202190 inde-pendent fashion. Moreover, LPA stimulated a dose-dependent and saturable phosphorylation of p38 MAPkinase, which was not altered by Y-27632 or C3 transfer-ase, a rho inactivator. These novel results suggest thatLPA stimulates hepatic myofibroblast migration via dis-tinct pathways that signal through rho and p38 MAPkinase.
- 中文關鍵字: --
- 英文關鍵字: Lysophosphatidic acid. Myosin. Liver. Rho-associated kinase. Phosphorylation. Contraction. Stress-activated protein kinase