| First Author | Lee EJ | Year | 2020 |
| Journal | J Exp Med | Volume | 217 |
| Issue | 6 | PubMed ID | 32267915 |
| Mgi Jnum | J:289545 | Mgi Id | MGI:6432739 |
| Doi | 10.1084/jem.20190402 | Citation | Lee EJ, et al. (2020) Hepatic stellate cell-specific knockout of transcriptional intermediary factor 1gamma aggravates liver fibrosis. J Exp Med 217(6) |
| abstractText | Transforming growth factor beta (TGFbeta) is a crucial factor in fibrosis, and transcriptional intermediary factor 1gamma (TIF1gamma) is a negative regulator of the TGFbeta pathway; however, its role in liver fibrosis is unknown. In this study, mesenchymal stem cells derived from human embryonic stem cells (hE-MSCs) that secrete hepatocyte growth factor (HGF) were used to observe the repair of thioacetamide (TAA)-induced liver fibrosis. Our results showed that TIF1gamma was significantly decreased in LX2 cells when exposed to TGFbeta1. Such decrease of TIF1gamma was significantly prevented by co-culture with hE-MSCs. Interaction of TIF1gamma with SMAD2/3 and binding to the promoter of the alpha-smooth muscle gene (alphaSMA) suppressed alphaSMA expression. Phosphorylation of cAMP response element-binding protein (CREB) and binding on the TIF1gamma promoter region induced TIF1gamma expression. Furthermore, hepatic stellate cell-specific TIF1gamma-knockout mice showed aggravation of liver fibrosis. In conclusion, loss of TIF1gamma aggravates fibrosis, suggesting that a strategy to maintain TIF1gamma during liver injury would be a promising therapeutic approach to prevent or reverse liver fibrosis. |
