title: The role of Resveratrol-induced mitophagy/autophagy in peritoneal mesothelial cells inflammatory injury via NLRP3 inflammasome activation triggered by mitochondrial ROS.
abstract: It has been suggested that continuous exposure of peritoneal mesothelial cells (PMCs) to high glucose-containing peritoneal dialysis (PD) solutions may result in peritoneal inflammatory injury and impairment of local peritoneal host defence. Here, we investigated the effect of glucose-based PD solutions on mitochondrial reactive oxygen species (ROS) and nod-like receptor 3 (NLRP3) inflammasome activation in human PMCs (HPMCs). Exposure of HPMCs to high glucose-based PD solutions resulted in ROS production, which can trigger NLRP3 activation, leading to IL-1β secretion. Additionally, resveratrol (RSV) treatment induced mitophagy/autophagy via adenosine monophosphate-activated protein kinase (AMPK) activation. Increased mitochondrial ROS concentrations and IL-1β upregulation were confirmed following inhibition (siRNA against Beclin1 and ATG5 or autophagy inhibitor 3MA), but not induction (RSV), of mitophagy/autophagy. Furthermore, we observed that ATG5 and Beclin1 downregulation sensitised cells to IL-1β release induced by MSU or nigericin, which is an NLRP3 inflammasome activator. RSV treatment attenuated this effect. Taken together, this study may provide a potential therapeutic strategy for peritoneal inflammatory injury via NLRP3 inflammasome activation triggered by mitochondrial ROS.
authors.affiliation: Departments of Nephrology, the Third Hospital of Wuhan, Wuhan University, Wuhan, Hubei 430074, China. Electronic address: doctorwujun@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Departments of Nephrology, the Third Hospital of Wuhan, Wuhan University, Wuhan, Hubei 430074, China.
authors.forename: Xiangyou
authors.initials: X
authors.lastname: Li
authors.affiliation: Departments of Nephrology, the Third Hospital of Wuhan, Wuhan University, Wuhan, Hubei 430074, China.
authors.forename: Geli
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Departments of Nephrology, the Third Hospital of Wuhan, Wuhan University, Wuhan, Hubei 430074, China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Departments of Nephrology, the Affiliated Yue Bei Hospital of Shantou University Medical College, Shaoguan, Guangdong 512026, China.
authors.forename: Min
authors.initials: M
authors.lastname: He
authors.affiliation: Departments of Nephrology, the Affiliated Yue Bei Hospital of Shantou University Medical College, Shaoguan, Guangdong 512026, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D063306:Mitophagy / Q000187:drug effects*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017382:Reactive Oxygen Species; D013267:Stilbenes; D000077185:Resveratrol
keywords: Mitophagy/autophagy; NLRP3; Peritoneal mesothelial cells; ROS; Resveratrol