1. Acute regulated expression of pendrin in human urinary exosomes
- Author
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Lydie Cheval, Carsten A. Wagner, Ganesh Pathare, Nasser A. Dhayat, Thomas J. Neuhaus, Nilufar Mohebbi, Daniel Guido Fuster, University of Zurich, Fuster, Daniel G, Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fluides Réactifs et Turbulence (IJLRDA-FRT), Institut Jean le Rond d'Alembert (DALEMBERT), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,Male ,MESH: Salt Stress ,MESH: Acidosis, Renal Tubular ,Physiology ,[SDV]Life Sciences [q-bio] ,Clinical Biochemistry ,030232 urology & nephrology ,1308 Clinical Biochemistry ,Exosomes ,Salt Stress ,Acid-base homeostasis ,10052 Institute of Physiology ,0302 clinical medicine ,MESH: Bicarbonates ,2737 Physiology (medical) ,Distal renal tubular acidosis ,Ingestion ,Homeostasis ,Urinary exosomes ,10035 Clinic for Nephrology ,MESH: Ammonia ,Receptor ,610 Medicine & health ,biology ,Chemistry ,Venous blood ,Acidosis, Renal Tubular ,Sulfate Transporters ,MESH: Homeostasis ,Adult ,medicine.medical_specialty ,Urinary system ,Acid–base homeostasis ,Excretion ,03 medical and health sciences ,Ammonia ,Physiology (medical) ,Internal medicine ,medicine ,otorhinolaryngologic diseases ,SLC26A4 ,Humans ,Pendrin ,MESH: Exosomes ,MESH: Humans ,MESH: Adult ,1314 Physiology ,medicine.disease ,MESH: Sulfate Transporters ,MESH: Male ,Bicarbonates ,030104 developmental biology ,Endocrinology ,biology.protein ,MESH: Biomarkers ,570 Life sciences ,Biomarkers - Abstract
International audience; It is well known that pendrin, an apical Cl-/HCO3-exchanger in type B intercalated cells, is modulated by chronic acid-base disturbances and electrolyte intake. To study this adaptation further at the acute level, we analyzed urinary exosomes from individuals subjected to oral acute acid, alkali, and NaCl loading. Acute oral NH4Cl loading (n = 8) elicited systemic acidemia with a drop in urinary pH and an increase in urinary NH4 excretion. Nadir urinary pH was achieved 5 h after NH4Cl loading. Exosomal pendrin abundance was dramatically decreased at 3 h after acid loading. In contrast, after acute equimolar oral NaHCO3 loading (n = 8), urinary and venous blood pH rose rapidly with a significant attenuation of urinary NH4 excretion. Alkali loading caused rapid upregulation of exosomal pendrin abundance at 1 h and normalized within 3 h of treatment. Equimolar NaCl loading (n = 6) did not alter urinary or venous blood pH or urinary NH4 excretion. However, pendrin abundance in urinary exosomes was significantly reduced at 2 h of NaCl ingestion with lowest levels observed at 4 h after treatment. In patients with inherited distal renal tubular acidosis (dRTA), pendrin abundance in urinary exosomes was greatly reduced and did not change upon oral NH4Cl loading. In summary, pendrin can be detected and quantified in human urinary exosomes by immunoblotting. Acid, alkali, and NaCl loadings cause acute changes in pendrin abundance in urinary exosomes within a few hours. Our data suggest that exosomal pendrin is a promising urinary biomarker for acute acid-base and volume status changes in humans.
- Published
- 2018