| First Author | Gao H | Year | 2022 |
| Journal | Cell Metab | Volume | 34 |
| Issue | 7 | Pages | 978-990.e4 |
| PubMed ID | 35700738 | Mgi Jnum | J:347563 |
| Mgi Id | MGI:7311470 | Doi | 10.1016/j.cmet.2022.05.008 |
| Citation | Gao H, et al. (2022) MiR-690 treatment causes decreased fibrosis and steatosis and restores specific Kupffer cell functions in NASH. Cell Metab 34(7):978-990.e4 |
| abstractText | Nonalcoholic steatohepatitis (NASH) is a liver disease associated with significant morbidity. Kupffer cells (KCs) produce endogenous miR-690 and, via exosome secretion, shuttle this miRNA to other liver cells, such as hepatocytes, recruited hepatic macrophages (RHMs), and hepatic stellate cells (HSCs). miR-690 directly inhibits fibrogenesis in HSCs, inflammation in RHMs, and de novo lipogenesis in hepatocytes. When an miR-690 mimic is administered to NASH mice in vivo, all the features of the NASH phenotype are robustly inhibited. During the development of NASH, KCs become miR-690 deficient, and miR-690 levels are markedly lower in mouse and human NASH livers than in controls. KC-specific KO of miR-690 promotes NASH pathogenesis. A primary target of miR-690 is NADK mRNA, and NADK levels are inversely proportional to the cellular miR-690 content. These studies show that KCs play a central role in the etiology of NASH and raise the possibility that miR-690 could emerge as a therapeutic for this condition. |
