Circ_0054633 silencing suppresses hyperglycemia-induced extracellular matrix accumulation in renal mesangial cells by regulating MiR-136-5p/SMAD3 signaling

Diabetic kidney disease (DKD) is the most common complication of diabetes mellitus (DM), with excessive deposition of the extracellular matrix (ECM) produced by glomerular mesangial cells being its critical hallmark. circ_0054633, a circular RNA, is a promising biomarker for DM; however, the role of this circular RNA in DKD remains unknown. This study enrolled 10 healthy controls (CT), 10 DM patients, and 10 DKD patients, and serum circ_0054633 expression was analyzed. Circ_0054633 levels gradually increased in the CT, DM, and DKD groups, which also correlated with the serum indicator albumin/urine creatinine ratio and the degree of fibrosis. <i>In</i> <i>vitro</i> experiments, circ_0054633 silencing markedly attenuated hyperglycemia stress-induced cell proliferation and ECM accumulation in human renal mesangial cells). <i>In vivo</i> experiments indicated that circ_0054633 silencing in the db/db mouse kidney suppressed renal fibrosis. Mechanistically, circ_0054633 silencing exerted its effect by releasing miR-136-5p, which then downregulated SMAD3. The present study possibly demonstrates the clinical significance of circ_0054633, which may be a target for future DKD treatment.