Acute regulated expression of pendrin in human urinary exosomes

Pathare, Ganesh Tukaram; Dhayat, Nasser; Mohebbi, Nilufar; Wagner, Carsten A.; Cheval, Lydie; Neuhaus, Thomas J.; Fuster, Daniel Guido (2018). Acute regulated expression of pendrin in human urinary exosomes. Pflügers Archiv : European journal of physiology, 470(2), pp. 427-438. Springer 10.1007/s00424-017-2049-0

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Nephrologie / Hypertonie
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Pathare, Ganesh Tukaram; Dhayat, Nasser and Fuster, Daniel Guido

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

1432-2013

Publisher:

Springer

Language:

English

Submitter:

Nasser Dhayat

Date Deposited:

07 Nov 2017 17:29

Last Modified:

25 Apr 2018 12:27

Publisher DOI:

10.1007/s00424-017-2049-0

PubMed ID:

28803436

Uncontrolled Keywords:

Pendrin . SLC26A4 . Acid-base homeostasis . Distal renal tubular acidosis . Urinary exosomes

BORIS DOI:

10.7892/boris.105296

URI:

https://boris.unibe.ch/id/eprint/105296

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