miR-199a-3p is involved in the pathogenesis and progression of diabetic neuropathy through downregulation of SerpinE2

Abstract

The present study aimed to investigate the expression status of miRNA-199a-3p in patients with diabetic neuropathy (DN) and the mechanism by which this miRNA is involved in the genesis of DN. The expression of miRNA-199a-3p in plasma of peripheral blood was compared between patients with diabetes and a family history of diabetes and control volunteers by reverse transcription-quantitative polymerase chain reaction (RT-qPCR); in 60 diabetes patients, 45 (75%) demosntrated upregulated miR-199a-3p expression compared with control volunteer plasma. RT-qPCR was also used to detect miRNA-199a-3p expression in paired lower limb skin tissues from 30 patients with DN and 20 control volunteers; miR-199a-3p expression in patients with DN was significantly higher than in the control group. Next miR-199a-3p expression levels were evaluated with respect to the clinic-pathological parameters of diabetes; increased expression of miR-199a-3p was significantly associated with increased disease duration (P=0.041), glycated hemoglobin (HbA1C) levels (P=0.033), and fibrinogen levels (P=0.003). Finally, the effects on downstream mRNA expression levels were investigated as a result of manipulating miR-199a-3p levels. miR-199a-3p overexpression inhibited the expression of the extracellular serine protease inhibitor E2 (SerpinE2). Therefore, it may be hypothesized that miR-199a-3p can induce DN via promoting coagulation in skin peripheral circulation, through the downregulation of SerpinE2. The present findings suggested that miR-199a-3p may have potential as a novel therapeutic target for the treatment of patients with DN.