Six-Transmembrane Epithelial Antigen of Prostate 3 Promotes Hepatic Insulin Resistance and Steatosis |
| |
| Institution: | 1. Department of Endocrinology, Huanggang Central Hospital, Huanggang, China;2. Department of Cardiovascular Surgery, Huanggang Central Hospital, Huanggang, China;3. Huanggang Institute of Translational Medicine, Huanggang Central Hospital, Huanggang, China;4. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China;5. Department of Stomatology, Huanggang Central Hospital, Huanggang, China |
| |
| Abstract: | Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by excessive deposition of fatty acids in the liver. Further deterioration leads to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma, creating a heavy burden on human health and the social economy. Currently, there are no effective and specific drugs for the treatment of NAFLD. Therefore, it is important to further investigate the pathogenesis of NAFLD and explore effective therapeutic targets for the prevention and treatment of the disease. Six-transmembrane epithelial antigen of prostate 3 (STEAP3), a STEAP family protein, is a metalloreductase. Studies have shown that it can participate in the regulation of liver ischemia-reperfusion injury, hepatocellular carcinoma, myocardial hypertrophy, and other diseases. In this study, we found that the expression of STEAP3 is upregulated in NAFLD. Deletion of STEAP3 inhibits the development of NAFLD in vivo and in vitro, whereas its overexpression promotes palmitic acid/oleic acid stimulation-induced lipid deposition in hepatocytes. Mechanistically, it interacts with transforming growth factor beta-activated kinase 1 (TAK1) to regulate the progression of NAFLD by promoting TAK1 phosphorylation and activating the TAK1-c-Jun N-terminal kinase/p38 signaling pathway. Taken together, our results provide further insight into the involvement of STEAP3 in liver pathology. |
| |
| Keywords: | STEAP3 metalloreductase NAFLD glucose metabolism disorder lipid deposition hepatic steatosis hepatocytes PA/OA TAK1 JNK/p38 signaling pathway GSEA"} {"#name":"keyword" "$":{"id":"kwrd0065"} "$$":[{"#name":"text" "_":"gene set enrichment analysis HCC"} {"#name":"keyword" "$":{"id":"kwrd0075"} "$$":[{"#name":"text" "_":"hepatocellular carcinoma HFD"} {"#name":"keyword" "$":{"id":"kwrd0085"} "$$":[{"#name":"text" "_":"high-fat diet iTAK1"} {"#name":"keyword" "$":{"id":"kwrd0095"} "$$":[{"#name":"text" "_":"inhibitor of TAK1 JNK"} {"#name":"keyword" "$":{"id":"kwrd0105"} "$$":[{"#name":"text" "_":"c-Jun N-terminal kinase KEGG"} {"#name":"keyword" "$":{"id":"kwrd0115"} "$$":[{"#name":"text" "_":"Kyoto Encyclopedia of Genes and Genomes NAFLD"} {"#name":"keyword" "$":{"id":"kwrd0125"} "$$":[{"#name":"text" "_":"nonalcoholic fatty liver disease NC"} {"#name":"keyword" "$":{"id":"kwrd0135"} "$$":[{"#name":"text" "_":"normal chow PA/OA"} {"#name":"keyword" "$":{"id":"kwrd0145"} "$$":[{"#name":"text" "_":"palmitic acid/oleic acid STEAP3"} {"#name":"keyword" "$":{"id":"kwrd0155"} "$$":[{"#name":"text" "_":"six-transmembrane epithelial antigen of prostate 3 TAK1"} {"#name":"keyword" "$":{"id":"kwrd0165"} "$$":[{"#name":"text" "_":"transforming growth factor beta-activated kinase 1 |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
