MiR-21 Protects Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Preventing Epithelial Cell Apoptosis and Inhibiting Dendritic Cell Maturation.

ABSTRACT: Renal tubular injury and innate immune responses induced by hypoxia contribute to acute kidney injury. Accumulating evidence suggests that miR-21 overexpression protects against kidney ischemia injury. Additionally, miR-21 emerges as a key inhibitor in dendritic cell maturation. Thus, we hypothesized that miR-21 protects the kidney from IR injury by suppressing epithelial cell damage and inflammatory reaction. In this study, we investigated effects of miR-21 and its signaling pathways (PTEN/AKT/mTOR/HIF, PDCD4/NF?-B) on kidney ischemia/reperfusion (IR) injury in vitro and in vivo. The results revealed that IR increased miR-21, HIF1?, and 2? expression in vivo and in vitro. MiR-21 interacted with HIF1? and 2? through the PTEN/AKT/mTOR pathway. Moreover, inhibition of miR-21 activated PDCD4/NF?-B pathways, which are critical for dendritic cell maturation. Renal IR triggers local inflammation by inducing the dendritic cell maturation and promoting the secretion of IL-12, IL-6, and TNF-? cytokines. Knockdown of miR-21 intensified the effect of IR on tubular epithelial cell apoptosis and dendritic cell maturation. Our results suggested that IR-inducible miR-21 protects epithelial cells from IR injury via a feedback interaction with HIF (PTEN/AKT/mTOR/HIF/miR-21) and by inhibiting maturation of DCs through the PDCD4/NF-?B pathway. These findings highlight new therapeutic opportunities in AKI.

SUBMITTER: Song N 

PROVIDER: S-EPMC6036242 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature