| First Author | Xu M | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 6384 |
| PubMed ID | 37821436 | Mgi Jnum | J:371354 |
| Mgi Id | MGI:7540065 | Doi | 10.1038/s41467-023-42040-9 |
| Citation | Xu M, et al. (2023) Tripartite motif containing 26 prevents steatohepatitis progression by suppressing C/EBPdelta signalling activation. Nat Commun 14(1):6384 |
| abstractText | Currently potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) and NASH-related pathopoiesis have failed to achieve expected therapeutic efficacy due to the complexity of the pathogenic mechanisms. Here we show Tripartite motif containing 26 (TRIM26) as a critical endogenous suppressor of CCAAT/enhancer binding protein delta (C/EBPdelta), and we also confirm that TRIM26 is an C/EBPdelta-interacting partner protein that catalyses the ubiquitination degradation of C/EBPdelta in hepatocytes. Hepatocyte-specific loss of Trim26 disrupts liver metabolic homeostasis, followed by glucose metabolic disorder, lipid accumulation, increased hepatic inflammation, and fibrosis, and dramatically facilitates NASH-related phenotype progression. Inversely, transgenic Trim26 overexpression attenuates the NASH-associated phenotype in a rodent or rabbit model. We provide mechanistic evidence that, in response to metabolic insults, TRIM26 directly interacts with C/EBPdelta and promotes its ubiquitin proteasome degradation. Taken together, our present findings identify TRIM26 as a key suppressor over the course of NASH development. |
