Bohnert, Bernhard N. and Daiminger, Sophie and Woern, Matthias and Sure, Florian and Staudner, Tobias and Ilyaskin, Alexandr V. and Batbouta, Firas and Janessa, Andrea and Schneider, Jonas C. and Essigke, Daniel and Kanse, Sandip and Haerteis, Silke and Korbmacher, Christoph and Artunc, Ferruh (2019) Urokinase-type plasminogen activator (uPA) is not essential for epithelial sodium channel (ENaC)-mediated sodium retention in experimental nephrotic syndrome. ACTA PHYSIOLOGICA, 227 (4): UNSP e1328. ISSN 1748-1708, 1748-1716
Full text not available from this repository. (Request a copy)Abstract
Aim In nephrotic syndrome, aberrantly filtered plasminogen (plg) is converted to active plasmin by tubular urokinase-type plasminogen activator (uPA) and thought to lead to sodium retention by proteolytic activation of the epithelial sodium channel (ENaC). This concept predicts that uPA is an important factor for sodium retention and that inhibition of uPA might be protective in nephrotic syndrome. Methods Activation of amiloride-sensitive currents by uPA and plg were studied in Xenopus laevis oocytes expressing murine ENaC. In doxorubicin-induced nephrotic mice, uPA was inhibited pharmacologically by amiloride and genetically by the use of uPA-deficient mice (uPA(-/-)). Results Experiments in Xenopus laevis oocytes expressing murine ENaC confirmed proteolytic ENaC activation by a combination of plg and uPA which stimulated amiloride-sensitive currents with concomitant cleavage of the ENaC gamma-subunit at the cell surface. Treatment of nephrotic wild-type mice with amiloride inhibited urinary uPA activity, prevented urinary plasmin formation and sodium retention. In nephrotic mice lacking uPA (uPA(-/-)), urinary plasmin formation from plg was suppressed and urinary uPA activity absent. However, in nephrotic uPA(-/-) mice, sodium retention was not reduced compared to nephrotic uPA(+/+) mice. Amiloride prevented sodium retention in nephrotic uPA(-/-) mice which confirmed the critical role of ENaC in sodium retention. Conclusion uPA is responsible for the conversion of aberrantly filtered plasminogen to plasmin in the tubular lumen in vivo. However, uPA-dependent plasmin generation is not essential for ENaC-mediated sodium retention in experimental nephrotic syndrome.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GAMMA-SUBUNIT; PROTEOLYTIC ACTIVATION; COLLECTING DUCT; ENAC; CLEAVAGE; ALDOSTERONE; MATURATION; SITES; Amiloride; epithelial sodium channel (ENaC); nephrotic syndrome; plasminogen; sodium retention; urokinase-type plasminogen activator |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Anatomie Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Molekulare und zelluläre Anatomie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Mar 2020 06:55 |
| Last Modified: | 24 Mar 2020 06:55 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25776 |
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