| First Author | Anavi S | Year | 2015 |
| Journal | Lab Invest | Volume | 95 |
| Issue | 8 | Pages | 914-24 |
| PubMed ID | 26097999 | Mgi Jnum | J:225739 |
| Mgi Id | MGI:5694293 | Doi | 10.1038/labinvest.2015.67 |
| Citation | Anavi S, et al. (2015) The role of iNOS in cholesterol-induced liver fibrosis. Lab Invest 95(8):914-24 |
| abstractText | 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-1alpha 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. |
