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Bohnert, B.N. ; Essigke, D.* ; Janessa, A.* ; Schneider, J.C.* ; Wörn, M.* ; Kalo, M.Z.* ; Xiao, M.* ; Kong, L.* ; Omage, K.* ; Hennenlotter, J.* ; Amend, B.* ; Birkenfeld, A.L. ; Artunc, F.

Experimental nephrotic syndrome leads to proteolytic activation of the epithelial sodium channel (ENaC) in the mouse kidney.

Am. J. Physiol.-Renal Physiol. 321, F480-F493 (2021)
Verlagsversion Postprint DOI PMC
Open Access Green
Proteolytic activation of the renal epithelial sodium channel ENaC involves cleavage events in its α- and γ-subunits and is thought to mediate sodium retention in nephrotic syndrome (NS). However, detection of proteolytically processed ENaC in kidney tissue from nephrotic mice has been elusive so far. We used a refined Western blot technique to reliably discriminate full-length α- and γ-ENaC and their cleavage products after proteolysis at their proximal and distal cleavage sites (designated from the N-terminus), respectively. Proteolytic ENaC activation was investigated in kidneys from mice with experimental NS induced by doxorubicin or inducible podocin deficiency with or without treatment with the serine protease inhibitor aprotinin. Nephrotic mice developed sodium retention and increased expression of fragments of α- and γ-ENaC cleaved at both the proximal and more prominently at the distal cleavage site, respectively. Treatment with aprotinin but not with the mineralocorticoid receptor antagonist canrenoate prevented sodium retention and upregulation of the cleavage products in nephrotic mice. Increased expression of cleavage products of α- and γ-ENaC was similarly found in healthy mice treated with a low salt diet, sensitive to mineralocorticoid receptor blockade. In human nephrectomy specimens, γ-ENaC was found in the full-length form and predominantly cleaved at its distal cleavage site. In conclusion, murine experimental NS leads to aprotinin-sensitive proteolytic activation of ENaC at both proximal and more prominently distal cleavage sites of its α- and γ-subunit, most likely by urinary serine protease activity or proteasuria.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Enac ; Epithelial Sodium Channel ; Nephrotic Syndrome ; Proteolysis ; Serine Proteases; Sodium-channel; Gamma-subunit; Enac; Maturation; Cleavage; Trafficking; Plasmin
ISSN (print) / ISBN 0002-9513
e-ISSN 1522-1466
Zeitschrift American Journal of Physiology - Renal Physiology
Quellenangaben Band: 321, Heft: 4, Seiten: F480-F493 Artikelnummer: , Supplement: ,
Verlag American Physiological Society
Verlagsort 9650 Rockville Pike, Bethesda, Md 20814 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)
Förderungen Deutsche Forschungsgemeinschaft (DFG)