title: Inhibiting MicroRNA-503 and MicroRNA-181d with Losartan Ameliorates Diabetic Nephropathy in KKAy Mice.
abstract: 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.
authors: Department of Nephrology, The First Hospital of China Medical University, Shenyang, Liaoning, China (mainland).
authors: XinWang
authors: X
authors: Zhu
authors: Department of Nephrology, The First Hospital of China Medical University, Shenyang, Liaoning, China (mainland).
authors: CongXiao
authors: C
authors: Zhang
authors: Department of Nephrology, The First Hospital of China Medical University, Shenyang, Liaoning, China (mainland).
authors: QiuLing
authors: Q
authors: Fan
authors: Department of Nephrology, The First Hospital of China Medical University, Shenyang, Liaoning, China (mainland).
authors: XiaoDan
authors: X
authors: Liu
authors: Department of Nephrology, The First Hospital of China Medical University, Shenyang, Liaoning, China (mainland).
authors: Gang
authors: G
authors: Yang
authors: Department of Nephrology, The First Hospital of China Medical University, Shenyang, Liaoning, China (mainland).
authors: Yi
authors: Y
authors: Jiang
authors: Department of Nephrology, The First Hospital of China Medical University, Shenyang, Liaoning, China (mainland).
authors: LiNing
authors: L
authors: Wang
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics
chemical_list: D035683:MicroRNAs; C556275:Mirn503 microRNA, mouse; C529100:mirn181 microRNA, mouse; D019808:Losartan