| First Author | Shafiei MS | Year | 2011 |
| Journal | Am J Pathol | Volume | 178 |
| Issue | 6 | Pages | 2690-9 |
| PubMed ID | 21641391 | Mgi Jnum | J:173291 |
| Mgi Id | MGI:5013832 | Doi | 10.1016/j.ajpath.2011.02.035 |
| Citation | Shafiei MS, et al. (2011) Adiponectin Regulation of Stellate Cell Activation via PPARgamma-Dependent and -Independent Mechanisms. Am J Pathol 178(6):2690-9 |
| abstractText | In this study, we elucidated the mechanism by which adiponectin modulates hepatic stellate cell activation and fibrogenesis. Adiponectin-overexpressing transgenic mice receiving thioacetamide were resistant to fibrosis, compared with controls. In contrast, adiponectin-null animals developed severe fibrosis. Expression of collagen alpha1(I) and alpha-smooth muscle actin (alpha-SMA) mRNAs were significantly lower in adiponectin-overexpressing mice, compared with controls. In wild-type stellate cells exposed to a lentivirus encoding adiponectin, expression of peroxisome proliferator-activated receptor-gamma (PPARgamma), SREBP1c, and CEBPalpha mRNAs was significantly increased (3.2-, 4.1-, and 2.2-fold, respectively; n = 3; P < 0.05, adiponectin virus versus control), consistent with possible activation of an adipogenic transcriptional program. Troglitazone, a PPARgamma agonist, strongly suppressed up-regulation of collagen alpha1(I) and alpha-SMA mRNA in stellate cells isolated from wild-type mice; however, stellate cells from adiponectin-null animals failed to respond to troglitazone. Furthermore, in isolated stellate cells in which PPARgamma was depleted using an adenovirus-Cre-recombinase system and in which adiponectin was also overexpressed, collagen alpha1(I) and alpha-SMA were significantly inhibited. We conclude that the PPARgamma effect on stellate cell activation and the fibrogenic cascade appears to be adiponectin-dependent; however, the inhibitory effect of adiponectin on stellate cell activation was not dependent on PPARgamma, suggesting the presence of PPARgamma-dependent as well as independent pathways in stellate cells. |
