title: Piezo1-dependent regulation of urinary osmolarity.
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 AVP-independent mechanism of urine dilution is also at play when fasting. Piezo1/2 are recently discovered essential components of the non-selective mechanically activated cationic channels. Using quantitative PCR analysis and taking advantage of a β-galactosidase 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 knock-down or conditional genetic deletion of Piezo1 specifically in renal cells fully suppresses activity of the stretch-activated non-selective 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 osmoregulation.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, UMR 7275 CNRS, Université de Nice Sophia Antipolis, Valbonne, France.
authors.forename: Joana Raquel
authors.initials: JR
authors.lastname: Martins
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, UMR 7275 CNRS, Université de Nice Sophia Antipolis, Valbonne, France.
authors.forename: David
authors.initials: D
authors.lastname: Penton
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, UMR 7275 CNRS, Université de Nice Sophia Antipolis, Valbonne, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Peyronnet
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, UMR 7275 CNRS, Université de Nice Sophia Antipolis, Valbonne, France.
authors.forename: Malika
authors.initials: M
authors.lastname: Arhatte
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, UMR 7275 CNRS, Université de Nice Sophia Antipolis, Valbonne, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Moro
authors.affiliation: Centre de Recherche des Cordeliers, CNRS ERL 8228, INSERM UMRS 1138, Université Pierre et Marie Curie, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Picard
authors.affiliation: Institute of Physiology, University of Regensburg, Regensburg, Germany.
authors.forename: Birgül
authors.initials: B
authors.lastname: Kurt
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, UMR 7275 CNRS, Université de Nice Sophia Antipolis, Valbonne, France.
authors.forename: Amanda
authors.initials: A
authors.lastname: Patel
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, UMR 7275 CNRS, Université de Nice Sophia Antipolis, Valbonne, France. honore@ipmc.cnrs.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Honoré
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, UMR 7275 CNRS, Université de Nice Sophia Antipolis, Valbonne, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Demolombe
mesh_terms: D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism; D001127:Arginine Vasopressin / Q000494:pharmacology; D002460:Cell Line; D003681:Dehydration / Q000378:metabolism / Q000503:physiopathology; D004231:Diuresis / Q000502:physiology; D007473:Ion Channels / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D051379:Mice; D009994:Osmolar Concentration; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology*
chemical_list: D051399:Aquaporin 2; D007473:Ion Channels; C552920:Piezo1 protein, mouse; D001127:Arginine Vasopressin
keywords: Collecting duct; Ion channels; Kidney; Mechanotransduction; Urea; Urine