Increased urinary excretion of the epithelial Na channel activator prostasin in patients with primary aldosteronism

Pizzolo, Francesca; Chiecchi, Laura; Morandini, Francesca; Castagna, Annalisa; Zorzi, Francesco; Zaltron, Chiara; Pattini, Patrizia; Chiariello, Carmela; Salvagno, Gian Luca; Olivieri, Oliviero

doi:10.1097/hjh.0000000000001168

Cited by 6 publications

(3 citation statements)

References 26 publications

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“…, ALIX, FC=0.65 [0.43–1.60]; TSG101, FC=0.66 [0.39–1.40]; CD63, FC=0.77 [0.34–1.29]) were also observed, implying changes in exosomal biogenesis and secretion. Although epithelial Na + channel subunits were not detected in this experiment, prostasin was identified in all uEV samples, which was an assumed indicator of full epithelial Na + channel activity/cleavage (22,23), but its level did not change during SSST.…”

Section: Resultsmentioning

confidence: 56%

Acute Intravenous NaCl and Volume Expansion Reduces Sodium-Chloride Cotransporter Abundance and Phosphorylation in Urinary Extracellular Vesicles

Wolley

et al. 2022

Kidney360

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Background:NaCl loading and volume expansion suppress the RAAS to reduce renal tubular reabsorption of NaCl and water, but effects on NCC and relevant renal transmembrane proteins that are responsible for this modulation in humans are less well investigated. Methods:We used uEVs as an indirect readout to assess renal transmembrane proteins involved in NaCl and water homeostasis in 44 hypertensive patients with repeatedly raised aldosterone-to-renin ratios undergoing infusion of 2L of 0.9% saline over 4 hours. Results:When measured by mass spectrometry in 13 patients, significant decreases were observed in NCC (median fold change (FC)=0.70), pendrin (FC=0.84), AQP2 (FC=0.62) and uEV markers including ALIX (FC=0.65) and TSG101 (FC=0.66). Immunoblotting reproduced the reduction in NCC (FC=0.54), AQP2 (FC=0.42), ALIX (FC=0.52) and TSG101 (FC=0.55) in the remaining 31 patients, and demonstrated a significant decrease in phosphorylated NCC (pNCC) (FC=0.49). However, after correction for ALIX, the reductions in NCC (FC=0.90) and pNCC (FC=1.00) were no longer apparent, while the significant decrease in AQP2 persisted (FC=0.62). Conclusions:We conclude that (1) decreases in NCC and pNCC induced by acute NaCl loading and volume expansion may be due to diluted post-test urines, (2) the lack of change of NCC and pNCC when corrected for ALIX despite a fall in plasma aldosterone may be due to the lack of change in plasma K+ and (3) the decrease in AQP2 may be due to a decrease in vasopressin in response to volume expansion.

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Section: Resultsmentioning

confidence: 56%

Acute Intravenous NaCl and Volume Expansion Reduces Sodium-Chloride Cotransporter Abundance and Phosphorylation in Urinary Extracellular Vesicles

Wolley

et al. 2022

Kidney360

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“…Rats delivered with an adenovirus-mediated human prostasin showed a marked increase in blood pressure and electrolyte imbalance [ 12 ]. Olivieri and coworkers proposed urinary prostasin as candidate marker for ENaC activation in human and reported a positive correlation between urinary prostasin concentration, increased urinary excretion of the epithelial Na + channel and primary aldosteronism [ 13 , 14 ]. Additionally, Li and coworkers reported an association of genetic variations of the prostasin gene with essential hypertension in the Xinjiang Kazakh ethnic population [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Kidney-Specific CAP1/Prss8-Deficient Mice Maintain ENaC-Mediated Sodium Balance through an Aldosterone Independent Pathway

Ehret

Jäger

Sergi

et al. 2022

IJMS

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The serine protease prostasin (CAP1/Prss8, channel-activating protease-1) is a confirmed in vitro and in vivo activator of the epithelial sodium channel ENaC. To test whether proteolytic activity or CAP1/Prss8 abundance itself are required for ENaC activation in the kidney, we studied animals either hetero- or homozygous mutant at serine 238 (S238A; Prss8cat/+ and Prss8cat/cat), and renal tubule-specific CAP1/Prss8 knockout (Prss8PaxLC1) mice. When exposed to varying Na+-containing diets, no changes in Na+ and K+ handling and only minor changes in the expression of Na+ and K+ transporting protein were found in both models. Similarly, the α- or γENaC subunit cleavage pattern did not differ from control mice. On standard and low Na+ diet, Prss8cat/+ and Prss8cat/cat mice exhibited standard plasma aldosterone levels and unchanged amiloride-sensitive rectal potential difference indicating adapted ENaC activity. Upon Na+ deprivation, mice lacking the renal CAP1/Prss8 expression (Prss8PaxLC1) exhibit significantly decreased plasma aldosterone and lower K+ levels but compensate by showing significantly higher plasma renin activity. Our data clearly demonstrated that the catalytic activity of CAP1/Prss8 is dispensable for proteolytic ENaC activation. CAP1/Prss8-deficiency uncoupled ENaC activation from its aldosterone dependence, but Na+ homeostasis is maintained through alternative pathways.

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“…Rats delivered with an adenovirus-mediated human prostasin showed a marked increase in blood pressure and electrolyte imbalance [12]. Olivieri and coworkers proposed urinary prostasin as candidate marker for ENaC activation in human and reported a positive correlation between urinary prostasin concentration, increased urinary excretion of the epithelial Na + channel and primary aldosteronism [13,14]. Additionally, Li and coworkers reported an association of genetic variations of the prostasin gene with essential hypertension in the Xinjiang Kazakh ethnic population [15].…”

Section: Introductionmentioning

confidence: 99%

Kidney-Specific CAP1/Prss8-Deficient Mice Maintain ENaC-Mediated Sodium Balance Through an Aldosterone Independent Pathway

Ehret,

Jäger,

Ino

et al. 2022

Journal of the American Society of Nephrology

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Increased urinary excretion of the epithelial Na channel activator prostasin in patients with primary aldosteronism

Cited by 6 publications

References 26 publications

Acute Intravenous NaCl and Volume Expansion Reduces Sodium-Chloride Cotransporter Abundance and Phosphorylation in Urinary Extracellular Vesicles

Acute Intravenous NaCl and Volume Expansion Reduces Sodium-Chloride Cotransporter Abundance and Phosphorylation in Urinary Extracellular Vesicles

Kidney-Specific CAP1/Prss8-Deficient Mice Maintain ENaC-Mediated Sodium Balance through an Aldosterone Independent Pathway

Kidney-Specific CAP1/Prss8-Deficient Mice Maintain ENaC-Mediated Sodium Balance Through an Aldosterone Independent Pathway

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