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

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 alpha 3 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 miRNAs, miR-124 expression demonstrated the greatest increase. Administration of miR-124 ASO for two weeks significantly reduced urinary podocytic nephrin, podocin and albumin excretion and up-regulate integrin a3 expression. Conclusion: MiR-124 is related to podocytic adhesive capacity damage and may be implicated in the pathogenesis of DN. Copyright (C) 2013 S. Karger AG, Basel