MicroRNA-132 controls water homeostasis through regulating MECP2-mediated vasopressin synthesis
| Autor: | Peter M.T. Deen, Patrick C.N. Rensen, Ton J. Rabelink, Coen van Solingen, Roel Bijkerk, Ruben G. de Bruin, Edwin O W Bredewold, Eric P. van der Veer, Barend W. Florijn, Benjamin D. Humphreys, Anton Jan van Zonneveld, Sander Kooijman, Rosa van den Berg, Christiane Trimpert |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Vasopressin Receptors Vasopressin Physiology Methyl-CpG-Binding Protein 2 Vasopressins vasopressin Hypothalamus Diuresis Gene Expression posttranscriptional regulation 03 medical and health sciences Internal medicine Gene expression medicine Gene silencing Animals Homeostasis Mice Inbred BALB C Aquaporin 2 microRNA Chemistry Reabsorption urogenital system Osmolar Concentration Apical membrane Water-Electrolyte Balance Arginine Vasopressin Mice Inbred C57BL MicroRNAs osmotic balance 030104 developmental biology Endocrinology Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] Osmoregulation hormones hormone substitutes and hormone antagonists |
| Zdroj: | American Journal of Physiology : Renal Physiology, 315, F1129-F1138 American Journal of Physiology : Renal Physiology, 315, 4, pp. F1129-F1138 |
| ISSN: | 1931-857X |
| Popis: | Contains fulltext : 196784.pdf (Publisher’s version ) (Closed access) 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. |
| Databáze: | OpenAIRE |
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