LINC00472通过miR-21-5p/STAT3轴调控糖尿病肾病进展

Abstract

Abstract To reveal the diagnostic value and regulatory role of LINC00472 in diabetic kidney disease (DKD). A total of 103 patients with type 2 diabetes mellitus (T2DM) and 111 patients with DKD were enrolled. Serum and urine samples were collected within 24 h of admission. Logistic regression predicted factors inducing DKD, while ROC analysis evaluated the diagnostic value of lncRNA for DKD. Gene expression was detected by RT-qPCR. Cell function was assessed using CCK-8 and Transwell assays. Cytokine concentrations were measured by ELISA. Dual luciferase reporter assays and RNA immunoprecipitation validated intergenic targeting relationships. LINC00472 was downregulated in DKD patients and high-glucose (HG)-induced human glomerular mesangial cells (HGMCs). LINC00472 demonstrated diagnostic value for DKD and correlated with renal function indicators (inverse correlation with serum creatinine and urine albumin-to-creatinine ratio; positive correlation with estimated glomerular filtration rate). Transfection of oe-LINC00472 inhibited HGMC function while reducing expression of fibrosis genes and inflammatory factors. miR-21-5p, a downstream target of LINC00472, was upregulated in DKD patients. A miR-21-5p mimic could reverse the protective effects of LINC00472 overexpression on HGMC cells. STAT3, a downstream target gene of the LINC00472/miR-21-5p axis involved in DKD, was downregulated in DKD patients and after HG treatment. Overexpression of LINC00472 suppresses HGMC cell dysfunction by sponging miR-21-5p, thereby inhibiting fibrosis and inflammation and ameliorating DKD progression.