Regulation of WNK1 expression by miR-192 and aldosterone

J Am Soc Nephrol. 2010 Oct;21(10):1724-31. doi: 10.1681/ASN.2009111186. Epub 2010 Sep 2.

Abstract

WNK1 and WNK4 encode two members of the WNK serine-threonine kinase subfamily. Greater WNK1 expression associates with higher BP. A combination of promoters, enhancers, repressors, and insulators regulate WNK1 expression, but whether microRNAs also modulate WNK1 expression is unknown. Here, computational analysis revealed the presence of a target sequence for miR-192 and miR-215 at the same site in the 3' untranslated region of the ubiquitous L- and the kidney-specific KS-WNK1. We functionally validated this target sequence by transient transfection and reporter assays. Although we observed expression of both miRs along the distal nephron, only miR-192 regulated endogenous WNK1 ex vivo. Furthermore, a potassium load, sodium depletion, and aldosterone infusion each significantly reduced miR-192 expression in the kidney. Taken together, these results suggest a miR-driven mechanism of gene regulation by aldosterone and a role for miR-192 in the regulation of sodium and potassium balance in the kidney.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Aldosterone / metabolism*
  • Animals
  • Base Sequence
  • Cell Line
  • Dogs
  • Kidney Tubules, Distal / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / metabolism*
  • Minor Histocompatibility Antigens
  • Potassium / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Sodium, Dietary / metabolism
  • WNK Lysine-Deficient Protein Kinase 1

Substances

  • 3' Untranslated Regions
  • MicroRNAs
  • Minor Histocompatibility Antigens
  • Mirn192 microRNA, mouse
  • Sodium, Dietary
  • Aldosterone
  • Protein Serine-Threonine Kinases
  • WNK Lysine-Deficient Protein Kinase 1
  • Wnk1 protein, mouse
  • Potassium