Abstract

Aims Podocyte injury is a hallmark of diabetic nephropathy (DN) and significantly contributes to disease progression. Accumulating evidence suggests that impaired autophagy exacerbates podocyte dysfunction under hyperglycaemic conditions. However, the underlying regulatory mechanisms remain incompletely understood. This study aimed to investigate the role and mechanism of microRNA-10a-5p (miR-10a-5p) in regulating podocyte injury and autophagy in DN. Methods The function of miR-10a-5p was explored in high glucose (HG)-induced murine podocyte (MPC5) cells and streptozotocin (STZ)-induced diabetic mice. Gain- and loss-of-function experiments were conducted using miR-10a-5p mimics or inhibitors. E2F transcription factor 7 (E2f7) was predicted as a downstream target of miR-10a-5p via bioinformatics, and the binding between miR-10a-5p and E2f7 was assessed using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Podocyte injury, cell apoptosis, inflammation and autophagy were assessed using flow cytometry, Western blotting, enzyme-linked immunosorbent assay (ELISA), transmission electron microscopy (TEM) and green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining. Rescue experiments were conducted by silencing or overexpressing E2f7 to confirm its role in miR-10a-5p–mediated effects. Results miR-10a-5p was significantly upregulated in HG-stimulated podocytes and kidney tissues of diabetic mice. Inhibition of miR-10a-5p alleviated HG-induced podocyte injury, as evidenced by enhanced cell viability, reduced apoptosis and inflammatory cytokine production, and restored autophagic activity. E2f7 was identified as a direct target of miR-10a-5p. Notably, silencing E2f7 abrogated the protective effects of miR-10a-5p inhibition on podocyte survival and autophagy, and E2f7 overexpression restored the detrimental effects of miR-10a-5p overexpression on podocytes. In vivo, administration of AntagomiR-10a-5p in STZ-induced diabeti