Background::Acute kidney injury (AKI) is a common complication in patients, especially elderly patients, who undergo cardiac surgery with cardiopulmonary bypass. Studies have indicated a protective role of autophagy in AKI. However, the mechanisms underlying the regulatory effect of autophagy in AKI among patients undergoing cardiac surgeries are poorly understood. In this study, we aimed to test the hypothesis that exosomal microRNAs (miRNAs) regulate autophagy in tubular epithelial cells after AKI.Methods::Plasma exosomal RNA was extracted from young and elderly AKI patients undergoing cardiac surgery, and the miRNAs expression during the perioperative period were analyzed using next-generation sequencing. The screened miRNAs and their target genes were subjected to gene oncology function and Kyoto Encyclopedia of Genes and Genome enrichment analyses. Renal tubular epithelial cell line (HK-2 cells) was cultured and hypoxia/reoxygenation (H/R) model was established, which is an in vitro renal ischemia/reperfusion (I/R) model. We used Western blot analysis, cell viability assay, transfection, luciferase assay to investigate the mechanisms underlying the observed increases in the levels of renal I/R injury-mediated exosomal miRNAs and their roles in regulating HK-2 cells autophagy. Results::miR-590-3p was highly enriched in the plasma exosomes of young AKI patients after cardiac surgery. Increased levels of miR-590-3p led to the increases in the expression of autophagy marker proteins, including Beclin-1 and microtubule associated protein 1 light chain 3 beta (LC3II), and prolonged the autophagic response in HK-2 cells after H/R treatment. These effects were achieved mainly via increases in the exosomal miR-590-3p levels, and the tumor necrosis factor receptor-associated factor 6 protein was shown to play a key role in I/R injury-mediated autophagy induction.Conclusion::Exosomes released from HK-2 cells after renal I/R injury regulate autophagy by transferring miR-590-3p in a paracrine manner, which suggests that increasing the miR-590-3p levels in HK-2 cell-derived exosomes may increase autophagy and protect against kidney injury after renal I/R injury.

Acute kidney injury;Autophagy;Exosome;Hypoxia;Ischemia;miR-590-3p;Reperfusion

Chen Yimeng;Zhang Congya;Du Yingjie;Yang Xiying;Liu Min;Yang Wenjing;Lei Guiyu;Wang Guyan

Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China;Weifang Medical University, School of Anesthesiology, Shandong Provincial Medicine and Health Key Laboratory of Clinical Anesthesia, Weifang, Shandong 261053, China

中华医学杂志（英文版）

[1]Chen Yimeng;Zhang Congya;Du Yingjie;Yang Xiying;Liu Min;Yang Wenjing;Lei Guiyu;Wang Guyan-.Exosomal transfer of microRNA-590-3p between renal tubular epithelial cells after renal ischemia-reperfusion injury regulates autophagy by targeting TRAF6)[J].中华医学杂志（英文版）,2022(20):2467-2477

Exosomal,3p,between,renal,tubular,epithelial,cells,after,ischemia,reperfusion,injury,regulates,autophagy,targeting,TRAF6,Background,Acute,kidney,AKI,common,complication,patients,especially,elderly,who,cardiac,surgery,cardiopulmonary,bypass,Studies,have,indicated,protective,However,mechanisms,underlying,regulatory,among,undergoing,surgeries,are,poorly,understood,this,study,aimed,test,hypothesis,that,exosomal,microRNAs,miRNAs,Methods,Plasma,was,extracted,from,young,expression,during,perioperative,period,were,analyzed,using,next,generation,sequencing,screened,their,genes,subjected,oncology,function,Kyoto,Encyclopedia,Genes,Genome,enrichment,analyses,Renal,line,HK,cultured,hypoxia,reoxygenation,model,established,which,vitro,used,blot,analysis,viability,assay,transfection,luciferase,investigate,observed,increases,levels,mediated,roles,regulating,Results,highly,enriched,plasma,exosomes,Increased,led,marker,proteins,including,Beclin,microtubule,associated,light,chain,beta,LC3II,prolonged,autophagic,response,treatment,These,effects,achieved,mainly,tumor,necrosis,receptor,shown,play,key,induction,Conclusion,Exosomes,released,transferring,paracrine,manner,suggests,increasing,derived,may,against,Autophagy,Hypoxia,Ischemia,Reperfusion

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