miR-193a as a potential mediator of WT-1/synaptopodin in the renoprotective effect of Losartan on diabetic kidney

Abstract

Diabetic nephropathy (DN) is the most common complication of diabetic patients, and has become a global healthcare problem. In this study, we used diabetic mice to evaluate the effect of Losartan on DN, in which the experimental animals were divided into three groups: non-diabetic mice (db/m group), untreated-diabetic mice (db/db group), and Losartan-treated diabetic mice (db/db-losartan). Next, immunohistochemistry and immunofluorescence were used to detect Wilms tumor protein 1 (WT-1) and synaptopodin expression, respectively. Protein levels of WT-1, synaptopodin, claudin1, and Pax-2 were assessed by Western blotting and real-time PCR. The miR-193a mRNA levels were quantitated by real-time PCR. The results showed that albuminuria was increased in diabetic mice compared with control animals and was significantly ameliorated by treatment with Losartan. In addition, Losartan significantly upregulated the immunopositive cell numbers of WT-1, the expression of WT-1 and synaptopodin in renal tissue. By contrast, expression of claudin1 and Pax-2 in renal tissue were decreased in db/db-losartan group. Besides, expression of miR-193a was decreased significantly in db/db-losartan group compared with the untreated diabetic group. Thus, Losartan has renoprotective effects on the control of tissue damage possibly by inhibiting the expression of miR-193a, thereby promoting the repair of podocyte injury in mice with DN.