Regulation of glomerular heparanase expression by aldosterone, angiotensin II and reactive oxygen species.
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Publication year
2009Source
Nephrology, Dialysis, Transplantation, 24, 9, (2009), pp. 2637-45ISSN
Publication type
Article / Letter to editor
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Organization
Nephrology
Surgery
Journal title
Nephrology, Dialysis, Transplantation
Volume
vol. 24
Issue
iss. 9
Page start
p. 2637
Page end
p. 45
Subject
N4i 4: Auto-immunity, transplantation and immunotherapy; NCMLS 1: Infection and autoimmunity; NCMLS 3: Tissue engineering and pathologyAbstract
BACKGROUND: Inhibition of the renin-angiotensin-aldosterone system (RAAS) provides renoprotection in adriamycin nephropathy (AN), along with a decrease in overexpression of glomerular heparanase. Angiotensin II (AngII) and reactive oxygen species (ROS) are known to regulate heparanase expression in vivo. However, it is unknown whether this is also the case for aldosterone. Therefore, we further assessed the role of aldosterone, AngII and ROS in the regulation of glomerular heparanase expression. METHODS: Six weeks after the induction of AN, rats were treated with vehicle (n = 8), lisinopril (75 mg/L, n = 10), spironolactone (3.3 mg/day, n = 12) or the combination of lisinopril and spironolactone (n = 14) for 12 weeks. Age-matched healthy rats served as controls (n = 6). After 18 weeks, renal heparanase and heparan sulfate (HS) expression were examined by immunofluorescence staining. In addition, the effect of aldosterone, AngII and ROS on heparanase expression in cultured podocytes was determined. RESULTS: Treatment with lisinopril, spironolactone or their combination significantly blunted the increased glomerular heparanase expression and restored the decreased HS expression in the GBM. Addition of aldosterone to cultured podocytes resulted in a significantly increased heparanase mRNA and protein expression, which could be inhibited by spironolactone. Heparanase mRNA and protein expression in podocytes were also significantly increased after stimulation with AngII or ROS. CONCLUSIONS: Our in vivo and in vitro results show that not only AngII and ROS, but also aldosterone is involved in the regulation of glomerular heparanase expression.
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- Faculty of Medical Sciences [90359]
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