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

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...

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Published in:American journal of physiology. Renal physiology 2018-10, Vol.315 (4), p.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: Article
Language:English
Subjects:
Aquaporins
Argipressin
Diuresis
Gene expression
Homeostasis
Hypothalamus
Intracerebroventricular administration
Kidneys
MeCP2 protein
Methyl-CpG binding protein
MicroRNAs
miRNA
Reabsorption
Vasopressin
Water balance
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Summary: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.
ISSN:1931-857X
1522-1466
DOI:10.1152/ajprenal.00087.2018