HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

The role of iNOS in cholesterol-induced liver fibrosis.

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.
AuthorsSarit Anavi, Michal Eisenberg-Bord, Michal Hahn-Obercyger, Olga Genin, Mark Pines, Oren Tirosh
JournalLaboratory investigation; a journal of technical methods and pathology (Lab Invest) Vol. 95 Issue 8 Pg. 914-24 (Aug 2015) ISSN: 1530-0307 [Electronic] United States
PMID26097999 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Cholesterol
  • Nitric Oxide Synthase Type II
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse
Topics
  • Animals
  • Cell Line
  • Cholesterol (toxicity)
  • DNA Damage (drug effects, genetics)
  • Diet, High-Fat
  • Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
  • Liver (drug effects, pathology)
  • Liver Cirrhosis (chemically induced, metabolism)
  • Male
  • Matrix Metalloproteinase 9 (metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nitric Oxide Synthase Type II (genetics, metabolism)
  • Rats

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: