Co-Authors:
Anavi, S., Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, Hebrew University of Jerusalem, PO Box 12, Rehovot, Israel
Eisenberg-Bord, M., Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, Hebrew University of Jerusalem, PO Box 12, Rehovot, Israel
Hahn-Obercyger, M., Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, Hebrew University of Jerusalem, PO Box 12, Rehovot, Israel
Genin, O., Institute of Animal Sciences, Volcani Center, Bet Dagan, Israel
Pines, M., Institute of Animal Sciences, Volcani Center, Bet Dagan, Israel
Tirosh, O., Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, Hebrew University of Jerusalem, PO Box 12, Rehovot, Israel
Abstract:
Accumulation of cholesterol in the liver is associated with the development of non-alcoholic steatohepatitis-related fibrosis. However, underlying mechanisms are not well understood. The present study investigated the role of inducible nitric oxide synthase (iNOS) in cholesterol-induced liver fibrosis by feeding wild-type (WT) and iNOS-deficient mice with control or high-cholesterol diet (HCD) for 6 weeks. WT mice fed with HCD developed greater liver fibrosis, compared with iNOS-deficient mice, as evident by Sirius red staining and higher expression levels of profibrotic genes. Enhanced liver fibrosis in the presence of iNOS was associated with hypoxia-inducible factor-1α stabilization, matrix metalloproteinase-9 expression, and enhanced hepatic DNA damage. The profibrotic role of iNOS was also demonstrated in vivo using a selective inhibitor of iNOS as well as in vitro in a rat liver stellate cell line (HSC-T6). In conclusion, these findings suggest that iNOS is an important mediator in HCD-induced liver fibrosis. © 2015 USCAP, Inc All rights reserved.
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