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

American Journal of Physiology. Renal Physiology
Roel BijkerkAnton Jan van Zonneveld

Abstract

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 regula...Continue Reading

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Citations

Feb 26, 2019·F1000Research·Marianna RanieriGiovanna Valenti
May 16, 2020·Communications Biology·Anton Jan van ZonneveldRoel Bijkerk
Jan 25, 2021·Archives of Biochemistry and Biophysics·Jiao WangKun Huang
May 4, 2021·Frontiers in Cardiovascular Medicine·Don M MatshaziTandi E Matsha

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Methods Mentioned

BETA
sedation
transfection
Assay
PCR

Software Mentioned

EchoMRI
ImageJ

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