MicroRNA-132 controls water homeostasis through regulating MECP2-mediated vasopressin synthesis

Roel Bijkerk, Christiane Trimpert, Coen van Solingen, Ruben G. de Bruin, Barend W. Florijn, Sander Kooijman, Rosa van den Berg, Eric P. van der Veer, Edwin O.W. Bredewold, Patrick C.N. Rensen, Ton J. Rabelink, Benjamin D. Humphreys, Peter M.T. Deen, Anton Jan van Zonneveld

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Fine-tuning of the body’s water balance is regulated by vasopressin (AVP), which induces the expression and apical membrane insertion of aquaporin-2 water channels and subsequent water reabsorption in the kidney. Here we demonstrate that silencing of microRNA-132 (miR-132) in mice causes severe weight loss due to acute diuresis coinciding with increased plasma osmolality, reduced renal total and plasma membrane expression of aquaporin-2, and abrogated increase in AVP levels. Infusion with synthetic AVP fully reversed the antagomir-132-induced diuresis, and low-dose intracerebroventricular administration of antagomir-132 similarly caused acute diuresis. Central and intracerebroventricular antagomir-132 injection both decreased hypothalamic AVP mRNA levels. At the molecular level, antagomir-132 increased the in vivo and in vitro mRNA expression of methyl-CpG-binding protein-2 (MECP2), which is a miR-132 target and which blocks AVP gene expression by binding its enhancer region. In line with this, treatment of hypothalamic N6 cells with a high-salt solution increased its miR-132 levels, whereas it attenuated endogenous Mecp2 mRNA levels. In conclusion, we identified miR-132 as a first miRNA regulating the osmotic balance by regulating the hypothalamic AVP gene mRNA expression.

Original languageEnglish
Pages (from-to)F1129-F1138
JournalAmerican Journal of Physiology - Renal Physiology
Issue number4
StatePublished - Oct 5 2018


  • Microrna
  • Osmotic balance
  • Posttranscriptional regulation
  • Vasopressin


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