| First Author | Choi S | Year | 2019 |
| Journal | Biochem Biophys Res Commun | Volume | 513 |
| Issue | 1 | Pages | 49-55 |
| PubMed ID | 30935693 | Mgi Jnum | J:291678 |
| Mgi Id | MGI:6443103 | Doi | 10.1016/j.bbrc.2019.03.156 |
| Citation | Choi S, et al. (2019) A novel STAT3 inhibitor, STX-0119, attenuates liver fibrosis by inactivating hepatic stellate cells in mice. Biochem Biophys Res Commun 513(1):49-55 |
| abstractText | Liver fibrosis is characterized by formation of scar tissue in the liver. The role of STAT3 signaling has been implicated on activating hepatic stellate cells (HSC) to myofibroblast-like cells in liver fibrosis. Major factors that activate STAT3 signaling are TGF-beta1 and IL-6, which are upregulated in the liver in patients afflicted with liver fibrosis. Recent reports indicate that not only IL-6, but also the non-canonical signaling pathway of TGF-beta1 is associated with STAT3 signaling. In this study, we demonstrate a new function of the STAT3 inhibitor, STX-0119, in liver fibrosis. STX-0119 is an inhibitor of STAT3 dimerization, which is required for nuclear localization of STAT3. We first investigated the anti-fibrotic effect of STX-0119 in in vitro experiments. Exposure to STX-0119 inhibited the nuclear localization of STAT3 in HSCs, resulting in decreased expression of its target genes, such as col1a1 and alphaSMA. In addition, STX-0119 also inhibited the TGF-beta1/IL-6-induced activation of HSCs. Next, we examined the in vivo effect of STX-0119 in the liver fibrosis mouse model using thioacetamide (TAA) and carbon tetrachloride (CCl4). STX-0119 attenuated the TAA-induced liver fibrosis by inhibiting activation of HSCs to myofibroblast-like cells. Consistent with the in vivo results using TAA-induced liver fibrosis model, treatment of STX-0119 similarly attenuated CCl4-induced liver fibrosis. In conclusion, we believe that STX-0119 inhibits the development of liver fibrosis by blocking the activation of hepatic stellate cells. These results indicate that STX-0119 is a potential new therapeutic strategy to prevent disease progression to cirrhosis. |
