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 contra ction by cultured rat hepatic stellate cells (HSCs) in association with the function of Rho-kinase, one of the target molecules of small GTPase Rho, B inding studies showed a single class-binding site of LPA on HSCs. LPA enhan ced the contraction of a collagen lattice seeded with HSCs, LPA increased t he number of HSCs with polygonal morphology that contained actin stress fib ers, and enhanced the phosphorylation of myosin light chain and the assembl y of focal adhesion kinase and RhoA around fibronectin-coated beads seeded on HSCs. The electric cell-substrate impedance sensor system showed that LP A enhanced adhesion of HSC to extracellular substrate. All the effects of L PA were suppressed by Y-27632, Rho-kinase inhibitor. These data support the notion that LPA is involved in modulating HSC morphology, its attachment t o surrounding extracellular matrix and its contraction by a mechanism invol ving Rho-kinase. (C) 2000 Academic Press.