RING finger 186 (RNF186) is involved in the process of endoplasmic reticulum (ER)-stress-mediated apoptosis and inflammation of different cell types, such as HeLa cells and colon epithelial cells. However, the physiological and functional roles of RNF186 in peripheral tissues remain largely unknown. In the current study, we investigate the physiological function of RNF186 in the regulation of ER stress with respect to its biological roles in regulating insulin sensitivity in mouse primary hepatocytes. RNF186 expression is induced in the livers of diabetic, obese and diet-induced obese (DIO) mice. Mouse primary hepatocytes were isolated and treated with Ad-RNF186 or Ad-GFP. The results suggest that overexpression of RNF186 increases the protein levels of the ER stress sensors inositol requiring kinase 1 (IRE1) and C/EBP homologous protein (CHOP) protein, as well as the phosphorylation level of eukaryotic initiation factor 2α (eIF2α), in mouse primary hepatocytes. This effect impedes the action of insulin through c-Jun N-terminal kinase (JNK)-mediated phosphorylation of insulin receptor substrate 1 (IRS1). Furthermore, overexpression of RNF186 also significantly increases the levels of proinflammatory cytokines, including TNFα, IL-6 and MCP1. In addition, tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, alleviates the expression of ER stress markers induced by RNF186 overexpression. Taken together, the results of the present study show that overexpression of RNF186 induces ER stress and impairs insulin signalling in mouse primary hepatocytes, suggesting that RNF186 merits further investigation as a potential therapeutic target for treatment of insulin-resistance-associated metabolic diseases.

无名指186（RNF186）参与内质网（ER）应激介导的凋亡和不同细胞类型（例如，HeLa细胞和结肠上皮细胞）的炎症过程。但是，RNF186在外周组织中的生理和功能作用仍然是未知的。在当前的研究中，我们就其在调节小鼠原代肝细胞胰岛素敏感性方面的生物学作用探讨了RNF186在调节ER应激中的生理功能。RNF186表达在糖尿病，肥胖和饮食诱导的肥胖（DIO）小鼠的肝脏中被诱导。分离小鼠原代肝细胞并用Ad-RNF186或Ad-GFP处理。结果表明，RNF186的过表达增加了内质网应激传感器肌醇中需要激酶1（IRE1）和C / EBP同源蛋白（CHOP）蛋白的蛋白水平，以及真核生物起始因子2α（eIF2α）的磷酸化水平。小鼠原代肝细胞。这种作用通过c-Jun N末端激酶（JNK）介导的胰岛素受体底物1（IRS1）磷酸化阻碍了胰岛素的作用。此外，RNF186的过表达也显着增加了促炎细胞因子的水平，包括TNFα，IL-6和MCP1。另外，内质网应激抑制剂tauroursodeoxycholic acid（TUDCA）减轻了由RNF186过表达诱导的内质网应激标志物的表达。在一起