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

• Published in: American journal of physiology. Renal physiology Vol. 315; no. 4; pp. F1129 - F1138
• Main Authors: Bijkerk, Roel, Trimpert, Christiane, van Solingen, Coen, de Bruin, Ruben G, Florijn, Barend W, Kooijman, Sander, van den Berg, Rosa, van der Veer, Eric P, Bredewold, Edwin O W, Rensen, Patrick C N, Rabelink, Ton J, Humphreys, Benjamin D, Deen, Peter M T, van Zonneveld, Anton Jan
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.10.2018
• Subjects: Aquaporins; Argipressin; Diuresis; Gene expression; Homeostasis; Hypothalamus; Intracerebroventricular administration; Kidneys; MeCP2 protein; Methyl-CpG binding protein; MicroRNAs; miRNA; Reabsorption; Vasopressin; Water balance; posttranscriptional regulation; microRNA; osmotic balance; vasopressin
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.00087.2018

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.