BACKGROUND
Diabetic nephropathy (DN) is the most lethal diabetic microvascular complication; it is a major cause of
renal failure, and an increasingly globally prominent healthcare problem. MATERIAL AND METHODS To identify susceptible
microRNAs for the pathogenesis of DN and the targets of
losartan treatment,
microRNA arrays were employed to survey the glomerular
microRNA expression profiles of KKAy mice treated with or without
losartan. KKAy mice were assigned to either a
losartan-treated group or a non-treatment group, with C57BL/6 mice used as a normal control. Twelve weeks
after treatment, glomeruli from the mice were isolated.
MicroRNA expression profiles were analyzed using
microRNA arrays. Real-time PCR was used to confirm the results. RESULTS
Losartan treatment improved
albuminuria and the pathological lesions of KKAy mice. The expression of 10
microRNAs was higher, and the expression of 12
microRNAs was lower in the glomeruli of the KKAy untreated mice than that of the CL57BL/6 mice. The expression of 4
microRNAs was down-regulated in the glomeruli of the KKAy
losartan-treated mice compared to that of the untreated mice. The expression of miRNA-503 and miRNA-181d was apparently higher in the glomeruli of the KKAy untreated mice, and was inhibited by
losartan treatment. CONCLUSIONS The over-expression of miR-503 and miR-181d in glomeruli of KKAy mice may be responsible for the pathogenesis of DN and are potential therapeutic targets for DN.