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MiR-590-3p Attenuates Acute Kidney Injury by Inhibiting Tumor Necrosis Factor Receptor-Associated Factor 6 in Septic Mice

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Abstract

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 β2-microglobulin (β2-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, β2-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.

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Acknowledgments

We give thanks to the Department of Pathology, Wuhan Third Hospital of Wuhan University to provide technical support.

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  1. Department of Emergency, Optics Valley hospital, Wuhan Third Hospital of Wuhan University, No. 216 Guanshan Road, Wuhan, 430073, China

    Jing Ma, Yu-tao Li, Shi-xiong Zhang, Shou-zhi Fu & Xian-zhi Ye

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  1. Jing Ma
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Correspondence to Shou-zhi Fu or Xian-zhi Ye.

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The experiment was approved by the Ethics Committee of the Wuhan three hospital of Wuhan University (Wuhan, China) and performed in accordance with its guidelines.

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Ma, J., Li, Yt., Zhang, Sx. et al. MiR-590-3p Attenuates Acute Kidney Injury by Inhibiting Tumor Necrosis Factor Receptor-Associated Factor 6 in Septic Mice. Inflammation 42, 637–649 (2019). https://doi.org/10.1007/s10753-018-0921-5

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