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Am J Physiol Gastrointest Liver Physiol 279: G304-G310, 2000;
0193-1857/00 $5.00
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Vol. 279, Issue 2, G304-G310, August 2000

Biological activities of novel lipid mediator sphingosine 1-phosphate in rat hepatic stellate cells

Hitoshi Ikeda1, Yutaka Yatomi2, Mikio Yanase1, Hiroaki Satoh1, Hisato Maekawa1, Itsuro Ogata1, Yukio Ozaki2, Yoh Takuwa3, Satoshi Mochida4, and Kenji Fujiwara4

1 First Department of Internal Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655; 2 Department of Laboratory Medicine, Yamanashi Medical University, Tamaho-chou, Nakakoma-gun, Yamanashi 409-3898; 3 Department of Physiology, Kanazawa University School of Medicine, 13-1 Takara-machi, Kanazawa 920-8640; and 4 Third Department of Internal Medicine, Saitama Medical School, 38 Moro-hongo, Moroyama-chou, Iruma-gun, Saitama 350-0495, Japan

Sphingosine 1-phosphate (S-1-P), a lipid mediator shown to be a ligand for G protein-coupled receptors (AGRs), endothelial differentiation gene (EDG)1, EDG3, and AGR16/EDG5, is stored in platelets and released on their activation. Platelet consumption occurs in acute liver injury. Hepatic stellate cells (HSCs) play an important role in wound healing. Effects of S-1-P on HSCs were investigated. S-1-P enhanced proliferation of culture-activated HSCs. The mitogenic effect was pertussis toxin sensitive, mitogen-activated protein kinase dependent, and more prominent at lower cell density. S-1-P increased contraction of collagen lattices containing HSCs, irrespective of activation state, in a C3 exotoxin-sensitive manner. mRNAs of EDG1 and AGR16, but not of EDG3, were detected in HSCs. In HSC activation, EDG1 mRNA levels were downregulated, whereas AGR16 mRNA levels were unchanged. Considering that HSCs are capable of production of extracellular matrices and modulation of blood flow in sinusoids, our results suggest that S-1-P may play a role in wound healing process in the liver.

endothelial differentiation gene 1; endothelial differentiation gene 3; aortic G protein-coupled receptor 16/endothelial differentiation gene 5; hepatic stellate cell activation


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