MiR-124 is Related to Podocytic Adhesive Capacity Damage in STZ-Induced Uninephrectomized Diabetic Rats

作者：Dong Li, Zhenyu Lu, Junya Jia, Zhenfeng Zheng, Shan Lin · 发表于：Kidney & Blood Pressure Research · 年份：2013 · DOI：10.1159/000355721 · 被引用次数：38 · 研究领域：Renal Diseases and Glomerulopathies、Chronic Kidney Disease and Diabetes、Genetic and Kidney Cyst Diseases

BACKGROUND: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Podocyte plays a key role in the pathogenesis of DN. Adhesive capacity damage of podocytes is characteristic in DN. Emerging evidence suggests that microRNAs (miRNAs) play crucial roles in controlling many cell adhesion molecules thus contribute to normal cell adhesion. The roles of miRNA in podocytic adhesive capacity damage in diabetic conditions remain largely unknown. METHODS: Diabetes was induced by tail vein injection of streptozotocin (STZ) into uninephrectomized male Wistar rats. Comparative miRNA expression array and real-time PCR analyses were conducted in sham group at week 0 (W0, n = 3) and STZ-induced uninephrectomized diabetic rats at week 1 (W1, n = 3) and week 2 (W2, n = 3) to demonstrate the greatest increased miRNA in renal cortex. At week 2, STZ-induced uninephrectomized diabetic rats were treated with vehicle (Group U, n = 9), chemically modified antisense RNA oligonucleotide (ASO) complementary to the mature miR-124 (Group O, n = 8), miR-124 mismatch control sequence (Group M, n = 8). Urine specimens were obtained for measurement of urine albumin concentration and urinary podocyte specific protein (nephrin and podocin) quantitation. Expression of integrin α3 were detected by immunohistochemistry and western blotting. RESULTS: MiRNAs are differentially regulated in renal cortex of STZ-induced uninephrectomized diabetic rats relative to sham rats. Among the up-regulated m...