Proteomics,Multiomics

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Quantitative proteomic analysis of urinary exosomes from patients with primary aldosteronism that underwent fludrocortisone suppression test


ABSTRACT: The sodium chloride cotransporters (NCC) and the epithelial sodium channel (ENaC) have been reported to be the main effectors of aldosterone in Na+ and Cl- reabsorption in the distal nephron and dietary K+ downregulates NCC. The Cl-/HCO3- exchanger pendrin has been revealed as a key role in maintaining extracellular fluid and electrolyte homeostasis by regulating Cl- reabsorption in the aldosterone-sensitive distal nephron working in tandem with ENaC and perhaps NCC. Pendrin-mediated Cl-/HCO3- exchange is stimulated in models of metabolic alkalosis (e.g. aldosterone administration or dietary NaHCO3 intake), and plasma K+ level is thought to negatively influence pendrin. In this study we used high-throughput proteomics and bioinformatics approaches to analyze urinary exosome contents isolated from patients undergoing fludrocortisone suppression test (FST, as a means of confirming or excluding primary aldosteronism [PA]) to examine the actions of administration of aldosterone analogs, NaCl and KCl orally on transmembrane proteins existing in urinary exosomes.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Urine

DISEASE(S): Conn's Syndrome

SUBMITTER: Qi Wu  

LAB HEAD: Robert A. Fenton

PROVIDER: PXD017083 | Pride | 2020-11-20

REPOSITORIES: Pride

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Publications

The Cl<sup>-</sup>/HCO<sub>3</sub><sup>-</sup> exchanger pendrin is downregulated during oral co-administration of exogenous mineralocorticoid and KCl in patients with primary aldosteronism.

Wu Aihua A   Wolley Martin J MJ   Wu Qi Q   Gordon Richard D RD   Fenton Robert A RA   Stowasser Michael M  

Journal of human hypertension 20201110 10


In primary aldosteronism (PA), the occurrence of K<sup>+</sup> loss and hypertension suggest alterations in renal tubular transport, but the molecular basis of these alterations in humans is unclear. In this study, urinary extracellular vesicles (uEVs) isolated from patients undergoing fludrocortisone suppression testing (FST, as a means of confirming or excluding PA) were analyzed using mass spectrometry-based proteomics to determine the combined effects of an aldosterone analogue, NaCl and KCl  ...[more]

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