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  • Title: MiR-132-3p activation aggravates renal ischemia-reperfusion injury by targeting Sirt1/PGC1alpha axis.
    Author: Li C, Han S, Zhu J, Cheng F.
    Journal: Cell Signal; 2023 Oct; 110():110801. PubMed ID: 37433399.
    Abstract:
    The pathogenesis of renal ischemic diseases remains unclear. In this study, we demonstrate the induction of microRNA-132-3p (miR-132-3p) in ischemic acute kidney injury (AKI) and cultured renal tubular cells under oxidative stress. miR-132-3p mimic increased apoptosis in renal tubular cells and enhanced ischemic AKI in mice, whereas miR-132-3p inhibition offered protective effects. We analyzed miR-132-3p target genes through bioinformatic analysis and Sirt1 was predicted as the target gene of miR-132-3p. Luciferase microRNA target reporter assay further verified Sirt1 as a direct target of miR-132-3p. In cultured tubular cells and mouse kidneys, IRI and H2O2 treatment repressed Sirt1 and PGC-1α/NRF2/HO-1 expression, whereas anti-miR-132-3p preserved Sirt1 and PGC-1α/NRF2/HO-1 expression. In renal tubular, Sirt1 inhibitor suppressed PGC1-1α/NRF2/HO-1 expression and aggravated tubular apoptosis. Together, the results suggest that miR-132-3p induction aggravates ischemic AKI and oxidative stress by repressing Sirt1 expression, and miR-132-3p inhibition offers renal protection and may be a potential therapeutic target.
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