Downregulation of mmu_circ_0000943 ameliorates renal ischemia reperfusion-triggered inflammation and oxidative stress via regulating mmu-miR-377-3p/Egr2 axis
International Immunopharmacology(2022)
Abstract
Background: Acute kidney injury (AKI) is a widely pathophysiological state triggered by renal ischemiareperfusion injury (IRI) during kidney transplant. Circular RNAs (circRNAs) have recently been shown to exert crucial roles in IRI. However, the underlying molecular mechanism is mainly undefined.Methods: Differentially expressed circRNAs between IRI and sham group were identified by analyzing RNA sequencing data in mice. Next, in vitro functional experiments were carried out to investigate the role of mmu_circ_0000943 in mouse kindey proximal tubule cell (TKPTS) apoptosis, inflammation response and oxidative stress using CCK-8, flow cytometry and ELISA assays, respectively. Moreover, bioinformatic prediction, western blot, luciferase reporter assay and RNA immunoprecipitation (RIP) were performed to examine the network among mmu_circ_0000943, miR-377-3p and early growth response 2 (Egr2).Results: Mmu_circ_0000943 was upregulated in renal IRI tissues and hypoxia/reoxygenation (H/R)-treated TKPTS cells. Knockdown of mmu_circ_0000943 inhibited cell apoptosis, inflammatory cytokine expression and oxidative stress upon H/R treatment. Mechanistically, co-transfection of siRNA targeting mmu_circ_0000943 and miR-377-3p inhibitor could counteract the anti-IRI effect. Furthermore, mmu_circ_0000943 regulated the expression of Egr2 by sponging miR-377-3p to alleviate H/R-induced TKPTS cell damage.Conclusion: This study suggested that mmu_circ_0000943 participated in progression of renal IRI by sponging miR-377-3p with Egr2, providing a new insight into AKI treatment.
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Key words
Acute kidney injury,Circular RNA,MicroRNA,Inflammation,Oxidative stress
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