MicroRNA-140-5p attenuated oxidative stress in Cisplatin induced acute kidney injury by activating Nrf2/ARE pathway through a Keap1-independent mechanism.

摘要: Abstract Oxidative stress was predominantly involved in the pathogenesis of acute kidney injury (AKI). Recent studies had reported protective role specific microRNAs (miRNAs) against oxidative stress. Hence, we investigated levels miR140-5p and its functional Cisplatin induced AKI. A mice induced-AKI model established. We found that miR-140-5p expression markedly increased kidney. Bioinformatics analysis revealed nuclear factor erythroid 2-related (Nrf2) a potential target miR-140-5p, demonstrated did not affect Kelch-like ECH-associated protein 1 (Keap1) level but directly targeted 3′-UTR Nrf2 mRNA played positive regulation which confirmed by luciferase activity assay western blot. What more, consistent with expression, Nrf2, as well antioxidant response element (ARE)-driven genes Heme Oxygenase-1 (HO-1) NAD(P)H:quinone oxidoreductase l (NQO1) were significantly tissues. In vitro study, Enforced HK2 cells attenuated decreasing ROS increasing manganese superoxide dismutase (MnSOD). Simultaneously, decreased lactate dehydrogenase (LDH) leakage improved cell vitality under Cisplatin-induced However, transfected siRNA targeting abrogated effects These results indicated might exert anti-oxidative function via Nrf2. Our findings showed novel transcriptional protected activating Nrf2-dependent pathway, providing potentially therapeutic injury.