Authors: Joana Raquel Martins David Penton Rémi Peyronnet Malika Arhatte Céline Moro Nicolas Picard Birgül Kurt Amanda Patel Eric Honoré Sophie Demolombe
Publish Date: 2016/03/29
Volume: 468, Issue: 7, Pages: 1197-1206
Abstract
The collecting duct CD is the final segment of the kidney involved in the fine regulation of osmotic and ionic balance During dehydration arginine vasopressin AVP stimulates the expression and trafficking of aquaporin 2 AQP2 to the apical membrane of CD principal cells thereby allowing water reabsorption from the primary urine Conversely when the secretion of AVP is lowered as for instance upon water ingestion or as a consequence of diabetes insipidus the CD remains water impermeable leading to enhanced diuresis and urine dilution In addition an AVPindependent mechanism of urine dilution is also at play when fasting Piezo1/2 are recently discovered essential components of the nonselective mechanically activated cationic channels Using quantitative PCR analysis and taking advantage of a βgalactosidase reporter mouse we demonstrate that Piezo1 is preferentially expressed in CD principal cells of the inner medulla at the adult stage unlike Piezo2 Remarkably siRNAs knockdown or conditional genetic deletion of Piezo1 specifically in renal cells fully suppresses activity of the stretchactivated nonselective cationic channels SACs Piezo1 in CD cells is dispensable for urine concentration upon dehydration However urinary dilution and decrease in urea concentration following rehydration are both significantly delayed in the absence of Piezo1 Moreover decreases in urine osmolarity and urea concentration associated with fasting are fully impaired upon Piezo1 deletion in CD cells Altogether these findings indicate that Piezo1 is critically required for SAC activity in CD principal cells and is implicated in urinary osmoregulationWe are grateful to the ANR 2008 du gène à la physiopathologie des maladies rares aux maladies communes to the ANR 2011 physiologie physiopathologie santé publique to the Fondation de la recherche médicale to the Fondation de recherche sur l’hypertension artérielle to the Fondation de France to the Association Française contre les Myopathies RP to the Association pour l’information et la recherche sur les maladies rénales génétiques France to the Région Provence Alpes Côte d’Azur to the Société Française d’hypertension artérielle to the Université de Nice Sophia Antipolis and to the CNRS for financial support JRM was a recipient of fellowship attributed by the LefoulonDelalande Fondation We are grateful to Dr Dorien Peters for sharing the KsprCre mice with us and to Dr Jacques Teulon for his help with the electrophysiology of isolated renal tubules
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