Lysophosphatidic acid enhances collagen gel contraction by hepatic stellate cells: association with rho-kinase.

We studied the effect of lysophosphatidic acid (LPA) on collagen gel contraction by cultured rat hepatic stellate cells (HSCs) in association with the function of Rho-kinase, one of the target molecules of small GTPase Rho. Binding studies showed a single class-binding site of LPA on HSCs. LPA enhanced the contraction of a collagen lattice seeded with HSCs. LPA increased the number of HSCs with polygonal morphology that contained actin stress fibers, and enhanced the phosphorylation of myosin light chain and the assembly of focal adhesion kinase and RhoA around fibronectin-coated beads seeded on HSCs. The electric cell-substrate impedance sensor system showed that LPA enhanced adhesion of HSC to extracellular substrate. All the effects of LPA were suppressed by Y-27632, Rho-kinase inhibitor. These data support the notion that LPA is involved in modulating HSC morphology, its attachment to surrounding extracellular matrix and its contraction by a mechanism involving Rho-kinase.

Yanase M ，Ikeda H ，Matsui A ，Maekawa H ，Noiri E ，Tomiya T ，Arai M ，Yano T ，Shibata M ，Ikebe M ，Fujiwara K ，Rojkind M ，Ogata I ... -  《BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS》

Y-27632, an inhibitor of rho-associated protein kinase, suppresses tumor cell invasion via regulation of focal adhesion and focal adhesion kinase.

Imamura F ，Mukai M ，Ayaki M ，Akedo H ... -  《-》

Involvement of Rho/Rho kinase pathway in regulation of apoptosis in rat hepatic stellate cells.

Ikeda H ，Nagashima K ，Yanase M ，Tomiya T ，Arai M ，Inoue Y ，Tejima K ，Nishikawa T ，Omata M ，Kimura S ，Fujiwara K ... -  《AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY》

Small GTP-binding protein, Rho, both increased and decreased cellular motility, activation of matrix metalloproteinase 2 and invasion of human osteosarcoma cells.

Matsumoto Y ，Tanaka K ，Harimaya K ，Nakatani F ，Matsuda S ，Iwamoto Y ... -  《-》

Increased contractility of hepatic stellate cells in cirrhosis is mediated by enhanced Ca2+-dependent and Ca2+-sensitization pathways.

Iizuka M ，Murata T ，Hori M ，Ozaki H ... -  《-》