Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 185, Issue 5, Pages 1423-1435Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2015.01.021
Keywords
-
Categories
Funding
- Canadian Institutes of Health Research (CIHR)
- Kidney Foundation of Canada (KFoC)
- Korea Research Foundation
- Korean Government (MOEHRD)
- Basic Research Promotion Fund [KRF-20100008732]
- Ontario Graduate Student Program
- KFoC
- Clinician Scientist Training Program at the University of Toronto
- Alberta Innovates [201200819] Funding Source: researchfish
Ask authors/readers for more resources
Blockade of the renin-angiotensin system attenuates the progression of experimental and clinical Alport syndrome (AS); however, the underlying mechanism(s) remains Largely unknown. We evaluated the renin-angiotensin system in 4- and 7-week-old homozygous for collagen, type IV, alpha 3 gene (Col4A3(-/-)) and wild-type mice, a model of AS characterized by proteinuria and progressive renal injury. Renal angiotensin (Ang) II levels increased, whereas renal Ang-(1-7) levels decreased in 7-week-old Col4a3(-/-) mice compared with age-matched controls; these changes were partially reversed by recombinant angiotensin-converting enzyme 2 (ACE2) treatment. The expression of both the angiotensinogen and renin protein increased in Col4a3(-/-) compared with wild-type mice. Consistent with the Ang-(1-7) levels, the expression and activity of kidney ACE2 decreased in 7-week-old Col4a3(-/-) mice. The urinary excretion rate of ACE2 paralleled the decline in tissue expression. Expression of an Ang II-induced gene, heme oxygenase-1, was up-regulated in the kidneys of 7-week-old Col4a3(-/-) mice compared with wild-type mice by microarray analysis. Heme oxygenase-1 (HO-1) protein expression was increased in kidneys of Col4a3(-/-) mice and normalized by treatment with ACE inhibitor. Urinary HO-1 excretion paralleled renal HO-1 expression. In conclusion, progressive kidney injury in AS is associated with changes in expression of intrarenal renin Ang system components and Ang peptides. HO-1 and ACE2 may represent novel markers of AS-associated kidney injury, whereas administration of recombinant ACE2 and/or Ang-(1-7) may represent novel therapeutic approaches in AS.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available