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1000 Titel
  • Proteolytic activation of the epithelial sodium channel (ENaC) by factor VII activating protease (FSAP) and its relevance for sodium retention in nephrotic mice
1000 Autor/in
  1. Artunc, Ferruh |
  2. Bohnert, Bernhard N. |
  3. Schneider, Jonas C. |
  4. Staudner, Tobias |
  5. Sure, Florian |
  6. Ilyaskin, Alexandr V. |
  7. Wörn, Matthias |
  8. Essigke, Daniel |
  9. Janessa, Andrea |
  10. Nielsen, Nis V. |
  11. Birkenfeld, Andreas L. |
  12. Etscheid, Michael |
  13. Haerteis, Silke |
  14. Korbmacher, Christoph |
  15. Kanse, Sandip M. |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-12-06
1000 Erschienen in
1000 Quellenangabe
  • 2022(474):217-229
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00424-021-02639-7 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766372 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Proteolytic activation of the epithelial sodium channel (ENaC) by aberrantly filtered serine proteases is thought to contribute to renal sodium retention in nephrotic syndrome. However, the identity of the responsible proteases remains elusive. This study evaluated factor VII activating protease (FSAP) as a candidate in this context. We analyzed FSAP in the urine of patients with nephrotic syndrome and nephrotic mice and investigated its ability to activate human ENaC expressed in Xenopus laevis oocytes. Moreover, we studied sodium retention in FSAP-deficient mice (Habp2-/-) with experimental nephrotic syndrome induced by doxorubicin. In urine samples from nephrotic humans, high concentrations of FSAP were detected both as zymogen and in its active state. Recombinant serine protease domain of FSAP stimulated ENaC-mediated whole-cell currents in a time- and concentration-dependent manner. Mutating the putative prostasin cleavage site in γ-ENaC (γRKRK178AAAA) prevented channel stimulation by the serine protease domain of FSAP. In a mouse model for nephrotic syndrome, active FSAP was present in nephrotic urine of Habp2+/+ but not of Habp2-/- mice. However, Habp2-/- mice were not protected from sodium retention compared to nephrotic Habp2+/+ mice. Western blot analysis revealed that in nephrotic Habp2-/- mice, proteolytic cleavage of α- and γ-ENaC was similar to that in nephrotic Habp2+/+ animals. In conclusion, active FSAP is excreted in the urine of nephrotic patients and mice and activates ENaC in vitro involving the putative prostasin cleavage site of γ-ENaC. However, endogenous FSAP is not essential for sodium retention in nephrotic mice.
1000 Sacherschließung
lokal FSAP-HABP2
lokal Factor VII activating protease
lokal Nephrotic syndrome
lokal Serine protease
gnd 4171469-6 Nephrotisches Syndrom
lokal Epithelial sodium channel (ENaC)
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0002-3777-9316|https://frl.publisso.de/adhoc/uri/Qm9obmVydCwgQmVybmhhcmQgTi4=|https://frl.publisso.de/adhoc/uri/U2NobmVpZGVyLCBKb25hcyBDLg==|https://frl.publisso.de/adhoc/uri/U3RhdWRuZXIsIFRvYmlhcw==|https://frl.publisso.de/adhoc/uri/U3VyZSwgRmxvcmlhbg==|https://frl.publisso.de/adhoc/uri/SWx5YXNraW4sIEFsZXhhbmRyIFYu|https://frl.publisso.de/adhoc/uri/V8O2cm4sIE1hdHRoaWFz|https://frl.publisso.de/adhoc/uri/RXNzaWdrZSwgRGFuaWVs|https://frl.publisso.de/adhoc/uri/SmFuZXNzYSwgQW5kcmVh|https://frl.publisso.de/adhoc/uri/TmllbHNlbiwgTmlzIFYu|https://frl.publisso.de/adhoc/uri/Qmlya2VuZmVsZCwgQW5kcmVhcyBMLg==|https://orcid.org/0000-0002-9974-1962|https://frl.publisso.de/adhoc/uri/SGFlcnRlaXMsIFNpbGtl|https://frl.publisso.de/adhoc/uri/S29yYm1hY2hlciwgQ2hyaXN0b3Bo|https://frl.publisso.de/adhoc/uri/S2Fuc2UsIFNhbmRpcCBNLg==
1000 Label
1000 Förderer
  1. Projekt DEAL |
  2. Deutsche Forschungsgemeinschaft |
  3. Norges Forskningsråd |
1000 Fördernummer
  1. -
  2. AR 1092/2–2; 387509280
  3. 251239
1000 Förderprogramm
  1. Open Access funding
  2. SFB 1350
  3. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Projekt DEAL |
    1000 Förderprogramm Open Access funding
    1000 Fördernummer -
  2. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm SFB 1350
    1000 Fördernummer AR 1092/2–2; 387509280
  3. 1000 joinedFunding-child
    1000 Förderer Norges Forskningsråd |
    1000 Förderprogramm -
    1000 Fördernummer 251239
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6431670.rdf
1000 Erstellt am 2022-02-18T09:44:09.749+0100
1000 Erstellt von 323
1000 beschreibt frl:6431670
1000 Bearbeitet von 25
1000 Zuletzt bearbeitet 2022-03-04T10:59:20.016+0100
1000 Objekt bearb. Fri Mar 04 10:58:49 CET 2022
1000 Vgl. frl:6431670
1000 Oai Id
  1. oai:frl.publisso.de:frl:6431670 |
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1000 Sichtbarkeit Daten public
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