Chronic angiotensin-converting enzyme inhibition up-regulates mouse kidney growth arrest specific-6 protein and the AXL subfamily of receptor tyrosine kinases
Introduction. Growth arrest specific-6 (GAS-6), a vitamin K-dependent protein, is a potential mediator in progressive and chronic renal disease, specifically as a mediator of abnormal mesangial cell proliferation. Nitric oxide and angiotensin II affect mesangial cell proliferation. However, an assoc...
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doaj-2591ebac97a546a3bced34bd7e1398b12021-05-02T19:21:19ZengHindawi - SAGE PublishingJournal of the Renin-Angiotensin-Aldosterone System1470-32032008-12-01910.1177/1470320308098342Chronic angiotensin-converting enzyme inhibition up-regulates mouse kidney growth arrest specific-6 protein and the AXL subfamily of receptor tyrosine kinases Pei Chia EngWendy Chen-Nee ChuaValerie Suk Peng ChewPeter Tsun Hon Wong Jian Lin YinBrett HamblyCraig Steven McLachlanIntroduction. Growth arrest specific-6 (GAS-6), a vitamin K-dependent protein, is a potential mediator in progressive and chronic renal disease, specifically as a mediator of abnormal mesangial cell proliferation. Nitric oxide and angiotensin II affect mesangial cell proliferation. However, an association between nitric oxide synthase or angiotensin II on GAS-6 expression in the kidney has not previously been examined. Thus, our aim was to examine the effects of antihypertensive angiotensin-converting enzyme inhibitors and chronic nitric oxide synthase inhibition on the kidney expression of GAS-6 and its receptors AXL, MER and RSE. Methods. Four groups of adult male C57BL/6J mice were studied: group 1, untreated controls (tap water for six weeks); group 2, treated orally with a nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME, 0.325 mg/ml for six weeks); group 3, treated orally with captopril (0.6875 mg/ml for six weeks); group 4, co-treated orally with L-NAME and captopril (same doses for six weeks).At the end of the study, kidneys were placed in fixative and processed to paraffin for immunohistochemical staining. Results. GAS-6 and its receptors were not present in control and L-NAME-treated mice. Positive GAS-6 staining was detectable only in those mice receiving some form of chronic dosing with captopril, whether they were treated with captopril only or with captopril and L-NAME. Immunohistochemical detection across cases for MER and RSE was rare, whereas AXL-positive staining in the kidney mirrored GAS-6 staining/expression.The staining of GAS6 and AXL was predominantly localised to the renal tubular cells. Conclusions. These findings suggest that GAS-6 may not be a final common pathway for nitric oxide synthase inhibition-induced renal disease. Renal tubular GAS-6 expression following captopril treatment was unexpected and could be beneficial in preventing tubular atrophy following the onset of persistent systemic hypertension.https://doi.org/10.1177/1470320308098342 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pei Chia Eng Wendy Chen-Nee Chua Valerie Suk Peng Chew Peter Tsun Hon Wong Jian Lin Yin Brett Hambly Craig Steven McLachlan |
spellingShingle |
Pei Chia Eng Wendy Chen-Nee Chua Valerie Suk Peng Chew Peter Tsun Hon Wong Jian Lin Yin Brett Hambly Craig Steven McLachlan Chronic angiotensin-converting enzyme inhibition up-regulates mouse kidney growth arrest specific-6 protein and the AXL subfamily of receptor tyrosine kinases Journal of the Renin-Angiotensin-Aldosterone System |
author_facet |
Pei Chia Eng Wendy Chen-Nee Chua Valerie Suk Peng Chew Peter Tsun Hon Wong Jian Lin Yin Brett Hambly Craig Steven McLachlan |
author_sort |
Pei Chia Eng |
title |
Chronic angiotensin-converting enzyme inhibition up-regulates mouse kidney growth arrest specific-6 protein and the AXL subfamily of receptor tyrosine kinases |
title_short |
Chronic angiotensin-converting enzyme inhibition up-regulates mouse kidney growth arrest specific-6 protein and the AXL subfamily of receptor tyrosine kinases |
title_full |
Chronic angiotensin-converting enzyme inhibition up-regulates mouse kidney growth arrest specific-6 protein and the AXL subfamily of receptor tyrosine kinases |
title_fullStr |
Chronic angiotensin-converting enzyme inhibition up-regulates mouse kidney growth arrest specific-6 protein and the AXL subfamily of receptor tyrosine kinases |
title_full_unstemmed |
Chronic angiotensin-converting enzyme inhibition up-regulates mouse kidney growth arrest specific-6 protein and the AXL subfamily of receptor tyrosine kinases |
title_sort |
chronic angiotensin-converting enzyme inhibition up-regulates mouse kidney growth arrest specific-6 protein and the axl subfamily of receptor tyrosine kinases |
publisher |
Hindawi - SAGE Publishing |
series |
Journal of the Renin-Angiotensin-Aldosterone System |
issn |
1470-3203 |
publishDate |
2008-12-01 |
description |
Introduction. Growth arrest specific-6 (GAS-6), a vitamin K-dependent protein, is a potential mediator in progressive and chronic renal disease, specifically as a mediator of abnormal mesangial cell proliferation. Nitric oxide and angiotensin II affect mesangial cell proliferation. However, an association between nitric oxide synthase or angiotensin II on GAS-6 expression in the kidney has not previously been examined. Thus, our aim was to examine the effects of antihypertensive angiotensin-converting enzyme inhibitors and chronic nitric oxide synthase inhibition on the kidney expression of GAS-6 and its receptors AXL, MER and RSE. Methods. Four groups of adult male C57BL/6J mice were studied: group 1, untreated controls (tap water for six weeks); group 2, treated orally with a nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME, 0.325 mg/ml for six weeks); group 3, treated orally with captopril (0.6875 mg/ml for six weeks); group 4, co-treated orally with L-NAME and captopril (same doses for six weeks).At the end of the study, kidneys were placed in fixative and processed to paraffin for immunohistochemical staining. Results. GAS-6 and its receptors were not present in control and L-NAME-treated mice. Positive GAS-6 staining was detectable only in those mice receiving some form of chronic dosing with captopril, whether they were treated with captopril only or with captopril and L-NAME. Immunohistochemical detection across cases for MER and RSE was rare, whereas AXL-positive staining in the kidney mirrored GAS-6 staining/expression.The staining of GAS6 and AXL was predominantly localised to the renal tubular cells. Conclusions. These findings suggest that GAS-6 may not be a final common pathway for nitric oxide synthase inhibition-induced renal disease. Renal tubular GAS-6 expression following captopril treatment was unexpected and could be beneficial in preventing tubular atrophy following the onset of persistent systemic hypertension. |
url |
https://doi.org/10.1177/1470320308098342 |
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