High-fat diet (HFD)-induced metabolic syndrome followed by chronic kidney disease (CKD) have received extensive attention. However, the pathogenesis that contributes to HFD-induced renal injury still remains unclear. Transmembrane protein 126B (Tmem126b) is a complex I assembly factor, playing critical role in controlling important biological processes. In the study, we showed that Tmem126b levels were increased in kidney of HFD-fed mice. Tmem126b knockout (KO) attenuated metabolic disorders in mice challenged with HFD. Further, Tmem126b-KO mice showed alleviated kidney damage in response to HFD treatment. Mechanistically, we suggested that in kidney of mice, the dyslipidemia, apoptosis, and mitochondria dysfunction generated by HFD were prevented by Tmem126b deletion via regulating the expression of associated signals. Further, we demonstrated that HFD-induced renal inflammation was ameliorated by Tmem126b knockout, as evidenced by the down-regulated expression of inflammatory factors, including tumor necrosis factor a (TNF-α), interleukin (IL)-6, IL-1β and monocyte chemotactic protein (MCP)-1, which was through repressing nuclear factor kappa B (NF-κB) signaling pathways. Additionally, Tmem126b ablation repressed oxidative stress in renal samples of HFD-fed mice partly by promoting nuclear factor-erythroid 2 related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) expression. The role of Tmem126b knockout in protecting against HFD-triggered renal injury was verified in palmitate (PA)-incubated cells with Tmem126b knockdown. Importantly, inhibiting Nrf-2 expression abolished Tmem126b knockdown-alleviated lipid deposition, apoptosis, inflammation, ROS generation and mitochondrial dysfunction. Collectively, our study identified Tmem126b as a positive regulator for the progression of CKD induced by HFD through meditating Nrf-2 expression.
Keywords: Apoptosis; Chronic kidney disease (CKD); Inflammation; ROS and Nrf-2; Tmem126b.
Copyright © 2018. Published by Elsevier Inc.