Deletion of the serine protease CAP2/Tmprss4 leads to dysregulated renal water handling upon dietary potassium depletion

Keppner, Anna; Maric, Darko; Sergi, Chloé; Ansermet, Camille; Bellis, Damien De; Kratschmar, Denise V.; Canonica, Jérémie; Klusoňová, Petra; Fenton, Robert A.; Odermatt, Alex; Crambert, Gilles; Hoogewijs, David; Hummler, Edith

doi:10.1038/s41598-019-55995-x

Cited by 14 publications

(14 citation statements)

References 78 publications

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“…When histidine kinase KdpD perceives K + limitation or salt stress, KdpD transfers the phosphoryl group to the response regulator KdpE and activates the high-affinity K + uptake system KdpFABC ( Heermann and Jung, 2010 ). On the contrary, the suppression of KdpD may inhibit the uptake of K + , which can destroy the intracellular homeostasis ( Keppner et al, 2019 ) and affect the osmotic pressure ( Sweet et al, 2020 ). Therefore, in this study, the down-regulation of kdpD might lead to the growth inhibition of Y. enterocolitica by this way.…”

Section: Resultsmentioning

confidence: 99%

Antibacterial and Antibiofilm Activities of Chlorogenic Acid Against Yersinia enterocolitica

et al. 2022

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Nowadays, developing new and natural compounds with antibacterial activities from plants has become a promising approach to solve antibiotic resistance of pathogenic bacteria. Chlorogenic acid (CA), as a kind of phenolic acid existing in many plants, has been found to process multifunctional activities including antibacterial activity. Herein, the antibacterial and antibiofilm activities of CA against Yersinia enterocolitica (Y. enterocolitica) were tested for the first time, and its mechanism of action was investigated. It was demonstrated that CA could exert outstanding antibacterial activity against Y. enterocolitica. Biofilm susceptibility assays further indicated that CA could inhibit biofilm formation and decrease the established biofilm biomass of Y. enterocolitica. It was deduced that through binding to Y. enterocolitica, CA destroyed the cell membrane, increased the membrane permeability, and led to bacterial cell damage. In addition, the transcriptomic analysis revealed that CA could disorder many physiological pathways, mainly including the ones of antagonizing biofilms and increasing cell membrane permeability. Finally, the spiked assay showed that the growth of Y. enterocolitica in milk was significantly inhibited by CA. Taken together, CA, as an effective bactericidal effector with application potential, exerts antagonistic activity against Y. enterocolitica by mainly intervening biofilm formation and membrane permeability-related physiological pathways.

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Section: Resultsmentioning

confidence: 99%

Antibacterial and Antibiofilm Activities of Chlorogenic Acid Against Yersinia enterocolitica

et al. 2022

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“…Under Na + restriction, amiloride-sensitive renal potential difference and ENaC-mediated sodium balance remained unchanged in vivo. 56 Overall, CAP2/Tmprss4 knockout mice did not seem to be directly implicated in the regulation and/or proteolytic ENaC activation.…”

Section: Cap2/tmprss4mentioning

confidence: 90%

ENaC activation by proteases

2022

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Proteases are fundamental for a plethora of biological processes, including signalling and tissue remodelling, and dysregulated proteolytic activity can result in pathogenesis. In this review, we focus on a subclass of membrane‐bound and soluble proteases that are defined as channel‐activating proteases (CAPs), since they induce Na+ ion transport through an autocrine mechanism when co‐expressed with the highly amiloride‐sensitive epithelial sodium channel (ENaC) in Xenopus oocytes. These experiments first identified CAP1 (channel‐activating protease 1, prostasin) followed by CAP2 (channel‐activating protease 2, TMPRSS4) and CAP3 (channel‐activating protease 3, matriptase) as in vitro mediators of ENaC current. Since then, more serine‐, cysteine‐ and metalloproteases were confirmed as in vitro CAPs that potentially cleave and regulate ENaC, and thus this nomenclature was not further followed, but is accepted as functional term or alias. The precise mechanism of ENaC modulation by proteases has not been fully elucidated. Studies in organ‐specific protease knockout models revealed evidence for their role in increasing ENaC activity, although the proteases responsible for ENaC activation are yet to be identified. We summarize recent findings in animal models of these CAPs with respect to their implication in ENaC activation. We discuss the consequences of dysregulated CAPs underlying epithelial phenotypes in pathophysiological conditions, and the role of selected protease inhibitors. We believe that these proteases may present interesting therapeutic targets for diseases with aberrant sodium homoeostasis.

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“…Extracted proteins for immune-based western blotting were first separated, according to molecular weight, using sodium dodecyl sulphate polyacrylamide gel-electrophoresis (SDS-PAGE) gels, followed by electrotransfer to nitrocellulose membranes (Amersham Hybond-ECL, GE Healthcare) as described before 54 , 55 . Equal amounts of protein and volume were loaded onto a 7.5% polyacrylamide gel for HIF-1α and HIF-2α, and 15% polyacrylamide gel for CYGB.…”

Section: Methodsmentioning

confidence: 99%

A reliable set of reference genes to normalize oxygen-dependent cytoglobin gene expression levels in melanoma

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Maric

Bosman

et al. 2021

Sci Rep

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Cytoglobin (CYGB) is a ubiquitously expressed protein with a protective role against oxidative stress, fibrosis and tumor growth, shown to be transcriptionally regulated under hypoxic conditions. Hypoxia-inducible CYGB expression is observed in several cancer cell lines and particularly in various melanoma-derived cell lines. However, reliable detection of hypoxia-inducible mRNA levels by qPCR depends on the critical choice of suitable reference genes for accurate normalization. Limited evidence exists to support selection of the commonly used reference genes in hypoxic models of melanoma. This study aimed to select the optimal reference genes to study CYGB expression levels in melanoma cell lines exposed to hypoxic conditions (0.2% O2) and to the HIF prolyl hydroxylase inhibitor roxadustat (FG-4592). The expression levels of candidate genes were assessed by qPCR and the stability of genes was evaluated using the geNorm and NormFinder algorithms. Our results display that B2M and YWHAZ represent the most optimal reference genes to reliably quantify hypoxia-inducible CYGB expression in melanoma cell lines. We further validate hypoxia-inducible CYGB expression on protein level and by using CYGB promoter-driven luciferase reporter assays in melanoma cell lines.

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Deletion of the serine protease CAP2/Tmprss4 leads to dysregulated renal water handling upon dietary potassium depletion

Cited by 14 publications

References 78 publications

Antibacterial and Antibiofilm Activities of Chlorogenic Acid Against Yersinia enterocolitica

Antibacterial and Antibiofilm Activities of Chlorogenic Acid Against Yersinia enterocolitica

ENaC activation by proteases

A reliable set of reference genes to normalize oxygen-dependent cytoglobin gene expression levels in melanoma

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