Lysophosphatidic Acid Enhances Collagen Gel Contraction by Hepatic Stellate Cells: Association with Rho-Kinase

doi:10.1006/bbrc.2000.3634

Biochemical and Biophysical Research Communications

Volume 277, Issue 1, 14 October 2000, Pages 72-78

https://doi.org/10.1006/bbrc.2000.3634 Get rights and content

Abstract

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.

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Citation Excerpt :
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^☆: Abbreviations used: LPA, lysophosphatidic acid; HSC, hepatic stellate cell; Y-27632, (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide; FAK, focal adhesion kinase; MLC, myosin light chain; ECIS, electric cell-substrate impedance sensor system.

¹: To whom correspondence and reprint requests should be addressed at Department of Gastroenterology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Fax: +81-3-5800-8806. E-mail: [email protected].

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Regular ArticleLysophosphatidic Acid Enhances Collagen Gel Contraction by Hepatic Stellate Cells: Association with Rho-Kinase☆

Abstract

Hepatic stellate cells

Seminars in medicine of the Beth Israel Hospital, Boston. The cellular basis of hepatic fibrosis. Mechanisms and treatment strategies

N. Engl. J. Med.

Hepatic fibrosis as wound repair: A progress report

J. Gastroenterol.

Lysophosphatidic acid: G-protein signalling and cellular responses

Curr. Opin. Cell Biol.

Diversity of cellular receptors and functions for the lysophospholipid growth factors lysophosphatidic acid and sphingosine 1-phosphate

FASEB J.

Phosphatidic acid that accumulates in platelet-derived growth factor-stimulated Balb/c 3T3 cells is a potential mitogenic signal

J. Biol. Chem.

Alpha2-adrenergic receptor-mediated release of lysophosphatidic acid by adipocytes. A paracrine signal for preadipocyte growth

J. Clin. Invest.

Secretory phospholipase A2 generates the novel lipid mediator lysophosphatidic acid in membrane microvesicles shed from activated cells

Cell

Lysophosphatidic acid mediates the rapid activation of platelets and endothelial cells by mildly oxidized low density lipoprotein and accumulates in human atherosclerotic lesions

Proc. Natl. Acad. Sci. USA

The small GTP-binding protein Rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors

Cell

Rho effectors and reorganization of actin cytoskeleton

FEBS Lett.

Rho-associated kinase, a novel serine/threonine kinase, as a putative target for the small GTP binding protein Rho

EMBO J.

The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase

EMBO J.

ROCK-I and ROCK-II, two isoforms of Rho-associated coiled-coil forming serine/threonine protein kinase in mice

FEBS Lett.

A novel serine/threonine kinase binding the Ras-related RhoA GTPase which translocates the kinase to peripheral membranes

J. Biol. Chem.

Formation of actin stress fibers and focal adhesions enhanced by Rho-kinase

Science

Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension

Nature

Relaxation of contracted rabbit tracheal and human bronchial smooth muscle by Y-27632 through inhibition of Ca2+ sensitization

Am. J. Respir. Cell Mol. Biol.

An essential part for Rho-associated kinase in the transcellular invasion of tumor cells

Nature Med.

Cytoskeletal rearrangements and transcriptional activation of c-fos serum response element by Rho-kinase

J. Biol. Chem.

Effects of lysophosphatidic acid on proliferation of stellate cells and hepatocytes in culture

Biochem. Biophys. Res. Commun.

Isolation and culture of hepatic lipocytes, Kupffer cells, and sinusoidal endothelial cells by density gradient centrifugation with Stractan

Anal. Biochem.

Regular Article
Lysophosphatidic Acid Enhances Collagen Gel Contraction by Hepatic Stellate Cells: Association with Rho-Kinase☆

Relaxation of contracted rabbit tracheal and human bronchial smooth muscle by Y-27632 through inhibition of Ca²⁺ sensitization