Acute regulated expression of pendrin in human urinary exosomes

Pathare, Ganesh; Dhayat, Nasser; Mohebbi, Nilufar; Wagner, Carsten A.; Cheval, Lydie; Neuhaus, Thomas J.; Fuster, Daniel

doi:10.1007/s00424-017-2049-0

Cited by 20 publications

(16 citation statements)

References 48 publications

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“…The effect of acid-base balance on renal pendrin expression in people has also been assessed by quantifying pendrin abundance in urinary exosomes following changes in acid-base balance. Pathare et al (138) observed that urinary pendrin exosome abundance falls with the acute oral administration of NH 4 Cl and rises with NaHCO 3 , consistent with observations in mice.…”

Section: Because Pendrin Mediates Renal Tubular Hcosupporting

confidence: 60%

The Renal Physiology of Pendrin-Positive Intercalated Cells

Wall

Verlander

Romero

2020

Physiological Reviews

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Intercalated cells (ICs) are found in the connecting tubule and the collecting duct. Of the three IC subtypes identified, type B intercalated cells are one of the best characterized and known to mediate Cl− absorption and HCO3− secretion, largely through the anion exchanger pendrin. This exchanger is thought to act in tandem with the Na+-dependent Cl−/HCO3− exchanger, NDCBE, to mediate net NaCl absorption. Pendrin is stimulated by angiotensin II and aldosterone administration via the angiotensin type 1a and the mineralocorticoid receptors, respectively. It is also stimulated in models of metabolic alkalosis, such as with NaHCO3 administration. In some rodent models, pendrin-mediated HCO3− secretion modulates acid-base balance. However, of probably more physiological or clinical significance is the role of these pendrin-positive ICs in blood pressure regulation, which occurs, at least in part, through pendrin-mediated renal Cl− absorption, as well as their effect on the epithelial Na+ channel, ENaC. Aldosterone stimulates ENaC directly through principal cell mineralocorticoid hormone receptor (ligand) binding and also indirectly through its effect on pendrin expression and function. In so doing, pendrin contributes to the aldosterone pressor response. Pendrin may also modulate blood pressure in part through its action in the adrenal medulla, where it modulates the release of catecholamines, or through an indirect effect on vascular contractile force. In addition to its role in Na+ and Cl− balance, pendrin affects the balance of other ions, such as K+ and I−. This review describes how aldosterone and angiotensin II-induced signaling regulate pendrin and the contribution of pendrin-positive ICs in the kidney to distal nephron function and blood pressure.

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Section: Because Pendrin Mediates Renal Tubular Hcosupporting

confidence: 60%

The Renal Physiology of Pendrin-Positive Intercalated Cells

Wall

Verlander

Romero

2020

Physiological Reviews

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“…These small intraluminal vesicles fuse with the plasma membrane of target cells when released into the extracellular environment ( 7 ). Exosomes can be detected in all bodily fluids, such as urine ( 8 ), seminal fluid ( 9 ), blood ( 10 ) and amniotic fluids ( 11 ). In the transmission of information and regulation of cell signal transduction between different cells, exosomes serve a significant role by selectively delivering biologically active substances to the target cells ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

A highly efficient method for isolating urinary exosomes

Zhu

Wang

et al. 2018

Int J Mol Med

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In the present study, a highly efficient method, referred to as optimized ultrafiltration (OUF), was developed. This method is effective for exosome purification and also facilitates clinical work involving substantial urinary exosome isolation. In the OUF method, 0.22-µm filters along with a dialysis membrane with a molecular weight cut-off of 10,000 kDa were introduced, in order to remove extracellular microvesicles that were >200 nm and concentrate the supernatant up to 1/50 of the initial volume. The existence, purity and production of the exosomes isolated by OUF and conventional ultracentrifugation (UC) were systematically compared by transmission electron microscopy, western blotting and nanoparticle tracking analysis. In addition, colloidal Coomassie-stained gel and reverse transcription-quantitative polymerase chain reaction were used to investigate the stability and integrity of exosomes isolated by these two protocols. The time required and cost of these two methods in the process of isolating urinary exosomes were also estimated. The results indicated that OUF clearly outperforms UC in quantity, quality and biological stability, and this improved method may have extensive applications in the growing fields of clinical biomarker discovery and exosome research.

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“…All study participants (men, aged 25–45 years) gave written informed consent, and the study protocol was approved by the ethics commission of the canton of Bern, or the Institutional Review Board of the University of Texas Southwestern Medical Center, Dallas, TX. Participants underwent the classical “short” NH 4 Cl loading test 21,23,24 and equimolar NaHCO 3 loading on separate days after overnight fasting and with at least 3 weeks between tests. All tests started at 8:00 AM, venous blood samples were obtained for chemistry, pH and blood gases at 8:00 AM, 10:00 AM, 12:00 PM.…”

Section: Methodsmentioning

confidence: 99%

Changes in V-ATPase subunits of human urinary exosomes reflect the renal response to acute acid/alkali loading and the defects in distal renal tubular acidosis

Pathare

Dhayat

Mohebbi

et al. 2018

Kidney International

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In the kidney, final urinary acidification is achieved by V-ATPases expressed in type A intercalated cells. The B1 subunit of the V-ATPase is required for maximal urinary acidification, while the role of the homologous B2 subunit is less clear. Here we examined the effect of acute acid/alkali loading in humans on B1 and B2 subunit abundance in urinary exosomes in normal individuals and of acid loading in patients with distal renal tubular acidosis (dRTA). Specificities of B1 and B2 subunit antibodies were verified by yeast heterologously expressing human B1 and B2 subunits, and murine wild-type and B1-deleted kidney lysates. Acute ammonium chloride loading elicited systemic acidemia, a drop in urinary pH, and increased urinary ammonium excretion. Nadir urinary pH was achieved at four to five hours, and exosomal B1 abundance was significantly increased at two through six hours after ammonium chloride loading. After acute equimolar sodium bicarbonate loading, blood and urinary pH rose rapidly, with a concomitant reduction of exosomal B1 abundance within two hours, which remained lower throughout the test. In contrast, no change in exosomal B2 abundance was found following acid or alkali loading. In patients with inherited or acquired distal RTA, the urinary B1 subunit was extremely low or undetectable and did not respond to acid loading in urine, whereas no change in B2 subunit was found. Thus, both B1 and B2 subunits of the V-ATPase are detectable in human urinary exosomes, and acid and alkali loading or distal RTA cause changes in the B1 but not B2 subunit abundance in urinary exosomes.

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Acute regulated expression of pendrin in human urinary exosomes

Cited by 20 publications

References 48 publications

The Renal Physiology of Pendrin-Positive Intercalated Cells

The Renal Physiology of Pendrin-Positive Intercalated Cells

A highly efficient method for isolating urinary exosomes

Changes in V-ATPase subunits of human urinary exosomes reflect the renal response to acute acid/alkali loading and the defects in distal renal tubular acidosis

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