Dysregulation of the miR-4286 in diabetic kidney disease and its role in inflammatory response

OBJECTIVE: We aimed to investigate the expression level and diagnostic value of miR-4286 in serum of DKD patients and validate its effect on podocyte inflammatory response and apoptosis in vitro. METHODS: We detected the expression level of serum miR-4286 and CADM1 in DKD patients and healthy individuals. Clinical correlations of miR-4286 with estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), and KDIGO risk categories were analyzed. We detected the expression change of miR-4286 in podocytes treated. ROC analysis was used to evaluate the diagnostic value of miR-4286. Dual-luciferase assay and RNA immunoprecipitation (RIP) were used to validate the targeting relationship between miR-4286 and CADM1. TNF-α and IL-1β in supernatants were detected by ELISA, CADM1 protein expression was assessed by Western blotting, and apoptosis was detected by flow cytometry. RESULTS: In DKD patients, upregulation of serum miR-4286 and downregulation of CADM1 were observed and negatively correlated. MiR-4286 levels were negatively correlated with eGFR, positively correlated with UACR, and increased across KDIGO risk categories. In vitro, mimicking diabetic conditions revealed that miR-4286 was upregulated and CADM1 was downregulated at both mRNA and protein levels in podocytes in HG group. Functionally, suppressing miR-4286 could ameliorate the HG-induced inflammation and apoptosis. While CADM1 knockdown aggravated both two kinds of damages. Importantly, suppressing CADM1 partly rescued the apoptosis from co-silencing miR-4286. CONCLUSION: This study demonstrated that miR-4286 could regulate inflammatory response and podocyte function in DKD by targeting CADM1. Upregulation of miR-4286 would suppress CADM1, further enhancing the release of inflammatory factors and apoptosis.