title: MiR-124 is related to podocytic adhesive capacity damage in STZ-induced uninephrectomized diabetic rats.
abstract: 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 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 α3 expression.
  
  
  CONCLUSIONS
  MiR-124 is related to podocytic adhesive capacity damage and may be implicated in the pathogenesis of DN.
authors.affiliation: Department of Nephrology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Lu
authors.forename: Junya
authors.initials: J
authors.lastname: Jia
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Zheng
authors.forename: Shan
authors.initials: S
authors.lastname: Lin
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000235:genetics / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009392:Nephrectomy; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: C548144:MIRN124 microRNA, rat; D035683:MicroRNAs