介导子单元MED1介导介导子共激活因子复合物与各种核受体的配体依赖性结合，并在胚胎发育、脂质和葡萄糖代谢、肝再生和肿瘤发生中发挥关键作用。然而，MED1在肝纤维化发展中的确切作用尚不清楚。在这里，我们展示了MED1在非酒精性脂肪肝（NASH）患者和小鼠的肝脏中表达增加，并与TGF-β信号传导和促纤维化因子呈正相关。经过CCl4处理后，在具有肝特异性MED1缺失（MED1ΔLiv）的小鼠中，肝纤维化要比MED1fl/fl小鼠少得多。在CCl4注射的MED1ΔLiv小鼠的肝脏中，抑制TGF-β/Smad2/3信号通路，减少纤维化标记物的基因表达，包括α平滑肌肌动蛋白（α-SMA），胶原蛋白1α1（Col1a1），基质金属蛋白酶-2（Mmp2）和金属蛋白酶抑制物1（Timp1）。转录组分析显示，CCl4处理的MED1ΔLiv小鼠的肝脏中的差异表达基因富集在氧化还原酶活性通路中，并且显著降低了与氧化还原酶活性相关的基因，例如Gm4756，Txnrd3和Etfbkmt。更重要的是，我们发现MED1敲除肝细胞中的氧化应激物的减少，阻断了LX2细胞中TGF-β/Smad2/3通路的激活和纤维化基因的表达。这些结果表明MED1是肝纤维化的正调节因子，MED1可能被视为肝纤维化逆转的潜在治疗靶点。

Mediator subunit MED1 mediates ligand-dependent binding of the Mediator coactivator complex to various nuclear receptors and plays critical role in embryonic development, lipid and glucose metabolism, liver regeneration and tumorigenesis. However, the precise role of MED1 in the development of liver fibrosis has been unclear. Here, we showed that MED1 expression was increased in livers from nonalcoholic steatohepatitis (NASH) patients and mice, and positively correlated with TGF-β signaling and pro-fibrotic factors. Upon with CCl4 treatment,hepatic fibrosis was much lesser in liver specific MED1 deletion (MED1ΔLiv) mice than in MED1fl/fl littermates. TGF-β/Smad2/3 signaling pathway was inhibited, and gene expression of fibrotic markers, including α-smooth muscle actin (α-SMA), collagen type 1 alpha 1 (Col1a1), matrix metalloproteinase-2 (Mmp2), and metallopeptidase inhibitor 1 (Timp1) were decreased in livers of MED1ΔLiv mice with CCl4 injection. Transcriptomic analysis revealed that the differentially expressed genes in livers of CCl4-adminstered MED1ΔLiv mice were enriched in pathway of oxidoreductase activity, following with robustly reduced oxidoreductase activity related genes, such as Gm4756, Txnrd3, and Etfbkmt. More importantly, we found that reduction of reactive oxygen species (ROS) in MED1knockdown hepatocytes blocked the activation of TGF-β/Smad2/3 pathway and the expression of fibrotic genes in LX2 cells. These results indicate that MED1 is a positive regulator for hepatic fibrogenesis and MED1 may be considered as a potential therapeutic target for the regression of liver fibrosis.