ArticleAmerican journal of physiology. Renal physiology2012
Tissue kallikrein activation of the epithelial Na channel.
Article in American journal of physiology. Renal physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 74 citations in OpenAlex.
- Kidney kallikrein-1 contributes to cleavage of γ-ENaC in vivo.American journal of physiology. Renal physiology · 2026Article
- Urokinase Promotes Redundantly Intratubular C3a-Formation But Not ENaC-Driven Hypertension in DOCA/Salt Kidney Injury.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Kidney kallikrein-1 contributes to cleavage of gamma-ENaCbioRxiv : the preprint server for biology · 2025Article
- Inhibition of mTORC2 promotes natriuresis in Dahl salt-sensitive rats via the decrease of NCC and ENaC activity.American journal of physiology. Renal physiology · 2024Article
- Influence of proteolytic cleavage of ENaC's γ subunit upon NaAmerican journal of physiology. Renal physiology · 2024Article
- Epithelial NaComprehensive Physiology · 2024Review
- Proteolytic Activation of the Epithelial Sodium Channel (ENaC): Its Mechanisms and Implications.International journal of molecular sciences · 2023Review
- Human Alpha-1 Antitrypsin Attenuates ENaC and MARCKS and Lowers Blood Pressure in Hypertensive Diabetic db/db Mice.Biomolecules · 2022Article
- Blood pressure effects of sodium transport along the distal nephron.Kidney international · 2022Review
- Transmembrane serine protease 2 (TMPRSS2) proteolytically activates the epithelial sodium channel (ENaC) by cleaving the channel's γ-subunit.The Journal of biological chemistry · 2022Article
- ENaC activation by proteases.Acta physiologica (Oxford, England) · 2022Review
- Increased endothelial sodium channel activity by extracellular vesicles in human aortic endothelial cells: putative role of MLP1 and bioactive lipids.American journal of physiology. Cell physiology · 2021Article
- Cleavage state of γENaC in mouse and rat kidneys.American journal of physiology. Renal physiology · 2021Article
- Transgenic Mice Overexpressing Human Alpha-1 Antitrypsin Exhibit Low Blood Pressure and Altered Epithelial Transport Mechanisms in the Inactive and Active Cycles.Frontiers in physiology · 2021Article
- Plasminogen Deficiency and Amiloride Mitigate Angiotensin II-Induced Hypertension in Type 1 Diabetic Mice Suggesting Effects Through the Epithelial Sodium Channel.Journal of the American Heart Association · 2020Article
- ENaC in Salt-Sensitive Hypertension: Kidney and Beyond.Current hypertension reports · 2020Review
- Aldosterone-dependent and -independent regulation of NaAmerican journal of physiology. Renal physiology · 2020Article
- Ubiquitination of renal ENaC subunits in vivo.American journal of physiology. Renal physiology · 2020Article
- Regulating ENaC's gate.American journal of physiology. Cell physiology · 2020Review
- Cathepsin B increases ENaC activity leading to hypertension early in nephrotic syndrome.Journal of cellular and molecular medicine · 2019Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
Epithelial Na Channels (ENaC) are responsible for the apical entry of Na(+) in a number of different epithelia including the renal connecting tubule and cortical collecting duct. Proteolytic cleavage of γ-ENaC by serine proteases, including trypsin, furin, elastase, and prostasin, has been shown to increase channel activity. Here, we investigate the ability of another serine protease, tissue kallikrein, to regulate ENaC. We show that excretion of tissue kallikrein, which is secreted into the lumen of the connecting tubule, is stimulated following 5 days of a high-K(+) or low-Na(+) diet in rats. Urinary proteins reconstituted in a low-Na buffer activated amiloride-sensitive currents (I(Na)) in ENaC-expressing oocytes, suggesting an endogenous urinary protease can activate ENaC. We next tested whether tissue kallikrein can directly cleave and activate ENaC. When rat ENaC-expressing oocytes were exposed to purified tissue kallikrein from rat urine (RTK), ENaC currents increased threefold in both the presence and absence of a soybean trypsin inhibitor (SBTI). RTK and trypsin both decreased the apparent molecular mass of cleaved cell-surface γ-ENaC, while immunodepleted RTK produced no shift in apparent molecular mass, demonstrating the specificity of the tissue kallikrein. A decreased effect of RTK on Xenopus ENaC, which has variations in the putative prostasin cleavage sites in γ-ENaC, suggests these sites are important in RTK activation of ENaC. Mutating the prostasin site in mouse γ-ENaC (γRKRK186QQQQ) abolished ENaC activation and cleavage by RTK while wild-type mouse ENaC was activated and cleaved similar to that of the rat. We conclude that tissue kallikrein can be a physiologically relevant regulator of ENaC activity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.