USP10 Alleviates Palmitic Acid-induced Steatosis through Autophagy in HepG2 Cells
| Autor: | Sheng-Liang Xin, Xiao-Li Pan, Xiao-Yuan Xu, Yan-Yan Yu |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Journal of Clinical and Translational Hepatology. :000-000 |
| ISSN: | 2310-8819 2225-0719 |
| DOI: | 10.14218/jcth.2022.00060 |
| Popis: | Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease caused by over-nutrition. Impaired autophagy is closely related to NAFLD progression. Recently, ubiquitin-specific peptidase-10 (USP10) was reported to ameliorate hepatic steatosis, but the underlying mechanism is still unclear. In view of the potential effects of USP10 on autophagy, we investigated whether USP10 alleviated steatosis through autophagy.HepG2 cells were treated with palmitic acid (PA) to model NAFLDPA induced cellular steatosis with dependance on autophagy. USP10 overexpression alleviated PA-induced steatosis, restored autophagic activity, promoted autophagic flux, including synthesis and degradation of autophagosomes, and lipid-targeted autophagy. In the presence of autophagy inhibitors, the protective effectiveness of USP10 on steatosis decreased. Furthermore, the specific inhibitor to C-jun N-terminal protein kinase-1 (JNK1), DB07268, abolished USP10-induced autophagy. However, during early stage inhibition of JNK1, compensatory expression of tuberous sclerosis complex-2 (TSC2) maintained autophagy. The degree of TSC2-to-JNK1 compensation was positively associated with USP10 level. Functionally, JNK1 and TSC2 were involved in the lipid-lowering effect of USP10.USP10 alleviated hepatocellular steatosis in autophagy-dependent manner. JNK1/TSC2 signaling pathways were required for USP10-induced autophagy. |
| Databáze: | OpenAIRE |
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