التفاصيل البيبلوغرافية
| العنوان: |
Mediator subunit MED1 deficiency prevents carbon tetrachloride-induced hepatic fibrosis in mice. |
| المؤلفون: |
Jie Gao, Miaoye Bao, Yuanming Xing, Yiming Ding, Tuo Han, Ergang Wen, Jun Liu, Shaoyun Yue, Rong Wang, Ling Wang, Junhui Liu, Sihai Zhao, Jiansheng Huang, Enqi Liu, Liang Bai |
| المصدر: |
American Journal of Physiology: Gastrointestinal & Liver Physiology; Nov2023, Vol. 325 Issue 5, pG418-G428, 11p |
| مصطلحات موضوعية: |
HEPATIC fibrosis, NUCLEAR receptors (Biochemistry), TRANSFORMING growth factors, GENE expression, REACTIVE oxygen species, NON-alcoholic fatty liver disease |
| مستخلص: |
Mediator subunit mediator 1 (MED1) mediates ligand-dependent binding of the mediator coactivator complex to various nuclear receptors and plays a 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 transforming growth factor β (TGF-β) signaling and profibrotic factors. Upon treatment with carbon tetrachloride (CCl4), hepatic fibrosis was much less 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 α 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-administered MED1ΔLiv mice were enriched in the pathway of oxidoreductase activity, followed by robustly reduced oxidoreductase activity-related genes, such as Gm4756, Txnrd3, and Etfbkmt. More importantly, we found that the reduction of reactive oxygen species (ROS) in MED1 knockdown 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. [ABSTRACT FROM AUTHOR] |
|
Copyright of American Journal of Physiology: Gastrointestinal & Liver Physiology is the property of American Physiological Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
