| First Author | Zhou Q | Year | 2014 |
| Journal | Biochim Biophys Acta | Volume | 1842 |
| Issue | 12 Pt A | Pages | 2367-77 |
| PubMed ID | 25305367 | Mgi Jnum | J:230463 |
| Mgi Id | MGI:5760109 | Doi | 10.1016/j.bbadis.2014.10.001 |
| Citation | Zhou Q, et al. (2014) GATA binding protein 2 mediates leptin inhibition of PPARgamma1 expression in hepatic stellate cells and contributes to hepatic stellate cell activation. Biochim Biophys Acta 1842(12 Pt A):2367-77 |
| abstractText | Hepatic stellate cell (HSC) activation is a crucial step in the development of liver fibrosis. Peroxisome-proliferator activated receptor gamma (PPARgamma) exerts a key role in the inhibition of HSC activation. Leptin reduces PPARgamma expression in HSCs and plays a unique role in promoting liver fibrosis. The present studies aimed to investigate the mechanisms underlying leptin regulation of PPARgamma1 (a major subtype of PPARgamma) in HSCs in vivo and in vitro. Results revealed a leptin response region in mouse PPARgamma1 promoter and indicated that the region included a GATA binding protein binding site around position -2323. GATA binding protein-2 (GATA-2) could bind to the site and inhibit PPARgamma1 promoter activity in HSCs. Leptin induced GATA-2 expression in HSCs in vitro and in vivo. GATA-2 mediated leptin inhibition of PPARgamma1 expression by its binding site in PPARgamma1 promoter in HSCs and GATA-2 promoted HSC activation. Leptin upregulated GATA-2 expression through beta-catenin and sonic hedgehog pathways in HSCs. Leptin-induced increase in GATA-2 was accompanied by the decrease in PPARgamma expression in HSCs and by the increase in the activated HSC number and liver fibrosis in vivo. Our data might suggest a possible new explanation for the promotion effect of leptin on liver fibrogenesis. |
