Clinical potential of miR-519d-3p in diabetic kidney disease and its regulatory mechanism on podocyte injury through targeting STAT3

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes. The clinical potential of miR-519d-3p in DKD and its function in podocyte injury were investigated, providing novel insight into the clinical management of DKD. A total of 117 DKD patients were included in the present study, with 93 diabetes patients as controls, and serum miR-519d-3p levels were compared between the two groups. The clinical value of miR-519d-3p was evaluated from the perspectives of diagnosis, severity assessment, and prognosis prediction. In vitro, a podocyte injury model was established by high-glucose stimulation. The effect of miR-519d-3p on cell viability, inflammation, oxidative stress, and fibrosis activation was evaluated. The involvement of STAT3 in the function of miR-519d-3p was assessed. miR-519d-3p was downregulated in DKD patients, which discriminated DKD patients from diabetes patients without DKD. Lower serum miR-519d-3p levels were observed in advanced DKD patients, and significant correlations were observed between miR-519d-3p and renal function of DKD patients. miR-519d-3p was revealed to be associated with the occurrence of ESRD in DKD patients, which was also identified as an independent risk factor. High glucose conditions induced podocyte injury and downregulation of miR-519d-3p, and overexpressing miR-519d-3p significantly attenuated high-glucose-induced injury. STAT3 was enriched as a direct target of miR-519d-3p related with DKD onset and progression. Its overexpression could reverse the protective effect of miR-519d-3p. Reducing serum miR-519d-3p can be considered a promising diagnostic and prognostic biomarker for DKD. Overexpressing the miR-519d-3p/STAT3 axis would be a promising therapeutic strategy for DKD.