Oxlund, Christina and Kurt, Birguel and Schwarzensteiner, Ilona and Hansen, Mie R. and Staehr, Mette and Svenningsen, Per and Jacobsen, Ib A. and Hansen, Pernille B. and Thuesen, Anne D. and Toft, Anja and Hinrichs, Gitte R. and Bistrup, Claus and Jensen, Boye L. (2017) Albuminuria is associated with an increased prostasin in urine while aldosterone has no direct effect on urine and kidney tissue abundance of prostasin. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 469 (5-6). pp. 655-667. ISSN 0031-6768, 1432-2013
Full text not available from this repository. (Request a copy)Abstract
The proteinase prostasin is a candidate mediator for aldosterone-driven proteolytic activation of the epithelial sodium channel (ENaC). It was hypothesized that the aldosterone-mineralocorticoid receptor (MR) pathway stimulates prostasin abundance in kidney and urine. Prostasin was measured in plasma and urine from type 2 diabetic patients with resistant hypertension (n = 112) randomized to spironolactone/placebo in a clinical trial. Prostasin protein level was assessed by immunoblotting in (1) human and rat urines with/without nephrotic syndrome, (2) human nephrectomy tissue, (3) urine and kidney from aldosterone synthase-deficient (AS(-/-)) mice and ANGII- and aldosterone-infused mice, and in (4) kidney from adrenalectomized rats. Serum aldosterone concentration related to prostasin concentration in urine but not in plasma. Plasma prostasin concentration increased significantly after spironolactone compared to control. Urinary prostasin and albumin related directly and were reduced by spironolactone. In patients with nephrotic syndrome, urinary prostasin protein was elevated compared to controls. In rat nephrosis, proteinuria coincided with increased urinary prostasin, unchanged kidney tissue prostasin, and decreased plasma prostasin while plasma aldosterone was suppressed. Prostasin protein abundance in human nephrectomy tissue was similar across gender and ANGII inhibition regimens. Prostasin urine abundance was not different in AS(-/-) and aldosterone-infused mice. Prostasin kidney level was not different from control in adrenalectomized rats and AS(-/-) mice. We found no evidence for a direct relationship between mineralocorticoid receptor signaling and kidney and urine prostasin abundance. The reduction of urinary prostasin in spironolactone-treated patients is most likely the result of an improved glomerular filtration barrier function and generally reduced proteinuria.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EPITHELIAL SODIUM-CHANNEL; SERINE-PROTEASE ACTIVITY; COLLECTING DUCT CELLS; SURFACE EXPRESSION; BLOOD-PRESSURE; RAT-KIDNEY; ACTIVATION; PLASMIN; MARKER; IDENTIFICATION; Epithelial sodium channel; Proteolysis; Adrenal; Nephrotic syndrome; Aldosterone synthase |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:10 |
| Last Modified: | 18 Feb 2019 12:49 |
| URI: | https://pred.uni-regensburg.de/id/eprint/805 |
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