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
M
Department of Gastroenterology, University of Tokyo, Tokyo, 113-0033, Japan.
Ikeda
H
H
Matsui
A
A
Maekawa
H
H
Noiri
E
E
Tomiya
T
T
Arai
M
M
Yano
T
T
Shibata
M
M
Ikebe
M
M
Fujiwara
K
K
Rojkind
M
M
Ogata
I
I
D000199:Actins / Q000378:metabolism; D000577:Amides / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D017097:Electric Impedance; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D005782:Gels / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D022502:Stress Fibers / Q000187:drug effects; D054460:rho-Associated Kinases
D000199:Actins; D000577:Amides; D005353:Fibronectins; D005782:Gels; D047908:Intracellular Signaling Peptides and Proteins; D008246:Lysophospholipids; D018994:Myosin Light Chains; D011725:Pyridines; C108830:Y 27632; D003094:Collagen; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases