| First Author | Fan K | Year | 2022 |
| Journal | Biochem Biophys Res Commun | Volume | 607 |
| Pages | 103-109 | PubMed ID | 35367821 |
| Mgi Jnum | J:325412 | Mgi Id | MGI:7266134 |
| Doi | 10.1016/j.bbrc.2022.03.110 | Citation | Fan K, et al. (2022) Immune response gene 1 deficiency impairs Nrf2 activation and aggravates liver fibrosis in mice. Biochem Biophys Res Commun 607:103-109 |
| abstractText | A growing body of evidence suggests that metabolic events play essential roles in the development of liver fibrosis. Immune response gene 1 (IRG1) catalyzes the generation of itaconate, which function as a metabolic checkpoint under several pathological circumstances. In the present study, the hepatic level of IRG1 was determined in mice with carbon tetrachloride (CCl4)-induced liver fibrosis. And then the pathological significance of IRG1 and the pharmacological potential of 4-octyl itaconate (4-OI), a cell-permeable derivate of itaconate, in liver fibrosis were investigated in mice. The results indicated that the hepatic level of IRG1 was upregulated in mice with liver fibrosis. CCl4-induced formation of fibrotic septa and deposition of collagen was aggravated in IRG1 KO mice. IRG1 deletion also resulted in increased expression of transforming growth factor beta 1 (TGF-beta1), enhanced phosphorylation of Smad3, elevated level of alpha smooth muscle actin (alpha-SMA) and hydroxyproline, which were associated with compromised activation of nuclear erythroid 2-related factor 2 (Nrf2)-mediated antioxidant system and exacerbated oxidative stress. Interestingly, supplementation with 4-OI activated Nrf2 pathway, suppressed TGF-beta1 signaling and attenuated fibrogenesis. Our data indicated that upregulation of IRG1 might function as a protective response during the development of liver fibrosis, and 4-OI might have potential value for the pharmacological intervention of liver fibrosis. |
