Background: Acute kidney injury (AKI) is a widely pathophysiological state triggered by renal ischemia-reperfusion 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.
Keywords: Acute kidney injury; Circular RNA; Inflammation; MicroRNA; Oxidative stress.
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