Dysregulation of kidney proteases in the pathogenesis of hypertension following unilateral nephrectomy in juvenile mice.

Autor:	Aly R; Department of Pediatrics, Division of Pediatric Nephrology, University of Florida College of Medicine Gainesville, FL, USA., Dogan YE; Department of Physiology and Aging, University of Florida College of Medicine Gainesville, FL, USA.; Department of Pediatrics, Faculty of Medicine, Erciyes University Kayseri, Turkey., Bala N; Department of Physiology and Aging, University of Florida College of Medicine Gainesville, FL, USA., Lugo C; Department of Physiology and Aging, University of Florida College of Medicine Gainesville, FL, USA., Darwish S; Department of Physiology and Aging, University of Florida College of Medicine Gainesville, FL, USA., Shoemaker L; Department of Pediatrics, Division of Pediatric Nephrology, University of Florida College of Medicine Gainesville, FL, USA., Alli AA; Department of Pediatrics, Division of Pediatric Nephrology, University of Florida College of Medicine Gainesville, FL, USA.; Department of Physiology and Aging, University of Florida College of Medicine Gainesville, FL, USA.; Department of Medicine, Division of Nephrology, Hypertension and Renal Transplantation, University of Florida College of Medicine Gainesville, FL, USA.
Jazyk:	angličtina
Zdroj:	American journal of translational research [Am J Transl Res] 2024 Feb 15; Vol. 16 (2), pp. 544-556. Date of Electronic Publication: 2024 Feb 15 (Print Publication: 2024).
Abstrakt:	Background: Unliteral nephrectomy (UNX) results in the reduction of kidney mass. The remaining kidney undergoes compensatory renal growth via hypertrophy of the glomeruli and renal tubules to maintain a normal glomerular filtration rate (GFR). These compensatory mechanisms result in increased capillary pressure and glomerular hyperfiltration to increase single nephron GFR. Over time, hyperfiltration may lead to kidney scarring and the development of hypertension. Objectives: The first objective of this study was to test the hypothesis that a 50% reduction in functioning nephrons in juvenile mice leads to increased blood pressure over a 24-hour phase. The second objective was to test the hypothesis that UNX leads to changes in the expression and activity of kidney proteases in juvenile mice. Methods: Eight male C57B6 juvenile wild-type mice were subject to UNX and an equal number of mice were subject to sham (SH) surgery. Metabolic cage studies were performed for 5 weeks to collect urine produced during the inactive and active phases. Blood pressure was measured using the tail cuff method twice weekly and tail blood was collected on different days during the inactive or active phase of each animal. The mice were euthanized at the age of 9 weeks. Western blotting and immunohistochemistry were performed to investigate changes in renal protein expression of various cathepsins and renal kallikrein 1 (KLK1) between the two groups. Protease activity assays were performed using kidney lysates and urine samples from each group. Results: Compared to the SH group, UNX mice showed a persistent increase in blood pressure at week 3 which progressed toward the end of the study at week 5 of age. Cathepsin B, D, and S expression and activity were up-regulated in kidney cortex lysates from UNX mice compared to the SH control group. KLK1 protein expression was down-regulated and urinary nitric oxide excretion was decreased in UNX mice compared to the SH control group. Conclusion: UNX results in the development of persistent and progressive hypertension. Down-regulation of KLK1 and up-regulation of various cathepsins may contribute to the development of hypertension via multiple mechanisms including a decrease in nitric oxide (NO) production. Competing Interests: None. (AJTR Copyright © 2024.)
Databáze:	MEDLINE
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