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

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 279; no. 2; pp. G304 - G310
• Main Authors: Ikeda, H, Yatomi, Y, Yanase, M, Satoh, H, Maekawa, H, Ogata, I, Ozaki, Y, Takuwa, Y, Mochida, S, Fujiwara, K
• Format: Journal Article
• Language: English
• Published: United States 01.08.2000
• Subjects: Actins - genetics; Animals; Anticoagulants - pharmacology; Blood Platelets - metabolism; Blotting, Northern; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell Division - drug effects; Cell Division - physiology; Cells, Cultured; Collagen - metabolism; DNA-Binding Proteins - genetics; Down-Regulation - physiology; Endothelium - cytology; Endothelium - metabolism; Gene Expression - drug effects; Gene Expression - physiology; GTP-Binding Proteins - genetics; GTP-Binding Proteins - metabolism; I-kappa B Proteins; Immediate-Early Proteins - genetics; Liver - cytology; Liver - metabolism; Liver Regeneration - physiology; Lysophospholipids; Male; NF-KappaB Inhibitor alpha; Pertussis Toxin; Platelet-Derived Growth Factor - pharmacology; Proto-Oncogene Proteins c-sis; Rats; Rats, Sprague-Dawley; Receptors, Cell Surface - genetics; Receptors, G-Protein-Coupled; Receptors, Lysophospholipid; RNA, Messenger - analysis; Sphingosine - analogs & derivatives; Sphingosine - pharmacology; Virulence Factors, Bordetella - pharmacology; Wound Healing - physiology
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.2000.279.2.g304

Sphingosine 1-phosphate (S-1-P), a lipid mediator shown to be a ligand for aortic G protein-coupled receptor [corrected] (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.