| First Author | Seo SH | Year | 2022 |
| Journal | Exp Mol Med | Volume | 54 |
| Issue | 9 | Pages | 1511-1523 |
| PubMed ID | 36114279 | Mgi Jnum | J:332457 |
| Mgi Id | MGI:7365657 | Doi | 10.1038/s12276-022-00851-8 |
| Citation | Seo SH, et al. (2022) Metabolic improvement and liver regeneration by inhibiting CXXC5 function for non-alcoholic steatohepatitis treatment. Exp Mol Med 54(9):1511-1523 |
| abstractText | Non-alcoholic steatohepatitis (NASH) is a chronic liver disease that results from multiple metabolic disorders. Considering the complexity of the pathogenesis, the identification of a factor mediating the multiple pathogenic phenotypes of NASH will be important for treatment. In this study, we found that CXXC5, a negative feedback regulator of the Wnt/beta-catenin pathway, was overexpressed with suppression of Wnt/beta-catenin signaling and its target genes involved in hepatic metabolism in obese-NASH patients. Cxxc5(-/-) mice were found to be resistant to NASH pathogenesis with metabolic improvements. KY19334, a small molecule that activates the Wnt/beta-catenin pathway via interference of the CXXC5-Dvl interaction, reversed the overall pathogenic features of NASH as Cxxc5(-/-) mice. The improvement in NASH by KY19334 is attributed to its regenerative effects through restorative activation of the suppressed Wnt/beta-catenin signaling. Overall, the pronounced metabolic improvements with the stimulation of liver regeneration by interfering with the CXXC5-Dvl interaction provide a therapeutic approach for NASH. |
