PMID- 30392071 OWN - NLM STAT- MEDLINE DCOM- 20190802 LR - 20200225 IS - 1573-2576 (Electronic) IS - 0360-3997 (Linking) VI - 42 IP - 2 DP - 2019 Apr TI - MiR-590-3p Attenuates Acute Kidney Injury by Inhibiting Tumor Necrosis Factor Receptor-Associated Factor 6 in Septic Mice. PG - 637-649 LID - 10.1007/s10753-018-0921-5 [doi] AB - Previous studies have been indicated that tumor necrosis factor receptor-associated factor 6 (TRAF6)-induced inflammation leads to acute kidney injury (AKI). How microRNA (miR) contributes to this process is poorly defined. The aim of this study was to investigate whether miR-590-3p regulated lipopolysaccharide (LPS)-induced inflammatory response by inhibiting TRAF6. LPS-induced septic mice were treated with adenovirus expressing miR-590-3p (ad-miR-590-3p) via tail-vein injection. AKI was evaluated by examining serum cystatin C (CysC), serum beta2-microglobulin (beta2-MG), and blood urea nitrogen (BUN). The mRNA and protein levels were assayed by RT-qPCR and western blotting, respectively. The proliferation of podocytes was monitored using the MTT assay. Cell apoptosis was analyzed by flow cytometry. Survival outcomes in ad-miR-590-3p-transfected septic mice were markedly improved compared with mice with LPS-induced sepsis. Ad-miR-590-3p transfection significantly attenuated LPS-induced AKI, which was reflected by an improved glomerular filtration rate (GFR) as determined by measuring CysC, beta2-MG, and BUN. Moreover, we observed that miR-590-3p was a novel regulator of TRAF6, binding to its 3'-untranslated regions (3'-UTRs). In vitro, a miR-590-3p gain-of-function mutation blocked LPS-induced podocyte growth inhibition and apoptosis, as well as overactivation of the inflammatory response. miR-590-3p has the ability to suppress LPS-induced AKI and podocyte apoptosis by targeting TRAF6. This might provide a novel strategy for the treatment of LPS-induced renal injuries. FAU - Ma, Jing AU - Ma J AD - Department of Emergency, Optics Valley hospital, Wuhan Third Hospital of Wuhan University, No. 216 Guanshan Road, Wuhan, 430073, China. FAU - Li, Yu-Tao AU - Li YT AD - Department of Emergency, Optics Valley hospital, Wuhan Third Hospital of Wuhan University, No. 216 Guanshan Road, Wuhan, 430073, China. FAU - Zhang, Shi-Xiong AU - Zhang SX AD - Department of Emergency, Optics Valley hospital, Wuhan Third Hospital of Wuhan University, No. 216 Guanshan Road, Wuhan, 430073, China. FAU - Fu, Shou-Zhi AU - Fu SZ AD - Department of Emergency, Optics Valley hospital, Wuhan Third Hospital of Wuhan University, No. 216 Guanshan Road, Wuhan, 430073, China. sz_futh@aliyun.com. FAU - Ye, Xian-Zhi AU - Ye XZ AD - Department of Emergency, Optics Valley hospital, Wuhan Third Hospital of Wuhan University, No. 216 Guanshan Road, Wuhan, 430073, China. xianzhi_ye123@163.com. LA - eng PT - Journal Article PL - United States TA - Inflammation JT - Inflammation JID - 7600105 RN - 0 (Lipopolysaccharides) RN - 0 (MIRN590 microRNA, mouse) RN - 0 (MicroRNAs) RN - 0 (TNF Receptor-Associated Factor 6) MH - Acute Kidney Injury/drug therapy/*prevention & control MH - Animals MH - Apoptosis MH - Inflammation/chemically induced MH - Lipopolysaccharides MH - Mice MH - MicroRNAs/*genetics MH - Podocytes/pathology MH - Sepsis/complications/*pathology MH - Survival Rate MH - TNF Receptor-Associated Factor 6/*antagonists & inhibitors OTO - NOTNLM OT - AKI OT - TRAF6 OT - apoptosis OT - inflammatory response OT - miR-590-3p OT - sepsis EDAT- 2018/11/06 06:00 MHDA- 2019/08/03 06:00 CRDT- 2018/11/05 06:00 PHST- 2018/11/06 06:00 [pubmed] PHST- 2019/08/03 06:00 [medline] PHST- 2018/11/05 06:00 [entrez] AID - 10.1007/s10753-018-0921-5 [pii] AID - 10.1007/s10753-018-0921-5 [doi] PST - ppublish SO - Inflammation. 2019 Apr;42(2):637-649. doi: 10.1007/s10753-018-0921-5.