Changes in microRNAs associated with podocytic adhesion damage under mechanical stress

J Renin Angiotensin Aldosterone Syst. 2013 Jun;14(2):97-102. doi: 10.1177/1470320312460071. Epub 2012 Oct 19.

Abstract

Introduction: Podocytes can respond to various injuries, including mechanical stress secondary to diabetic nephropathy (DN), which may cause deleterious adhesive effects on podocytes. Integrin α3β1 is the major podocyte adhesion molecule. In this study, we aim to investigate α3β1 expression and identify differentially expressed microRNAs in podocytes under mechanical stress compared with normal cells and podocytes under mechanical stress treated with spironolactone, respectively.

Materials and methods: Serum and glucocorticoid induced kinase 1 (SGK1), mineralocorticoid receptor (MR) and integrin α3β1 were detected by Western blotting. The miRNA analyses were performed by TaqMan MicroRNA Array v2.0. Genes Itga3 and Itgb1 were analyzed for miRNA binding sites within 3'UTRs using TargetScan and PicTar.

Results: Protein SGK1 and MR expression were significantly increased under mechanical stress and decreased after spironolactone treatment. Podocyte α3 and β1 expression were significantly decreased under mechanical stress and increased after spironolactone treatment. MiR-124, miR-190, miR-217 and miR-188 were the overlapped miRNAs that were upregulated under mechanical stress and downregulated after spironolactone treatment. MiR-124 was found to be a predicted miRNA target site in both Itga3 and Itgb1 3'UTRs.

Conclusion: These results provide a novel idea that miR-124 might play an important role in podocytic adhesion damage under mechanical stress.

Keywords: Integrin; diabetic nephropathy; mechanical stress; microRNA; podocyte.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Aldosterone / metabolism
  • Base Sequence
  • Cell Adhesion / drug effects
  • Cell Adhesion / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Line
  • Computational Biology
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Humans
  • Integrin alpha3beta1 / genetics
  • Integrin alpha3beta1 / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Podocytes / cytology*
  • Podocytes / drug effects
  • Podocytes / metabolism*
  • Protein Serine-Threonine Kinases / metabolism
  • Receptors, Mineralocorticoid / genetics
  • Receptors, Mineralocorticoid / metabolism
  • Spironolactone / pharmacology
  • Stress, Mechanical*
  • Up-Regulation / drug effects

Substances

  • 3' Untranslated Regions
  • Cell Adhesion Molecules
  • Integrin alpha3beta1
  • MicroRNAs
  • Receptors, Mineralocorticoid
  • Spironolactone
  • Aldosterone
  • Protein Serine-Threonine Kinases
  • serum-inducible kinase