The Role of Adrenomedullin in the Renal NADPH Oxidase and (Pro)renin in Diabetic Mice

Adrenomedullin has an antioxidative action and protects organs in various diseases. To clarify the role of adrenomedullin in diabetic nephropathy, we investigated the NADPH oxidase expression, renin-secreting granular cell (GC) hyperplasia, and glomerular matrix expansion in the streptozotocin (STZ)...

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Main Authors: Michio Hayashi, Akihiro Tojo, Tatsuo Shimosawa, Toshiro Fujita
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2013/134395
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author Michio Hayashi
Akihiro Tojo
Tatsuo Shimosawa
Toshiro Fujita
author_facet Michio Hayashi
Akihiro Tojo
Tatsuo Shimosawa
Toshiro Fujita
author_sort Michio Hayashi
collection DOAJ
description Adrenomedullin has an antioxidative action and protects organs in various diseases. To clarify the role of adrenomedullin in diabetic nephropathy, we investigated the NADPH oxidase expression, renin-secreting granular cell (GC) hyperplasia, and glomerular matrix expansion in the streptozotocin (STZ)-induced diabetic adrenomedullin gene knockout (AMKO) mice compared with the STZ-diabetic wild mice at 10 weeks. The NADPH oxidase p47phox expression and lipid peroxidation products were enhanced in the glomeruli of the diabetic mice compared with that observed in the controls in both wild and AMKO mice. These changes were more obvious in the AMKO mice than in the wild mice. Glomerular mesangial matrix expansion was more severe in the diabetic AMKO mice than in the diabetic wild mice and exhibited a positive correlation with the degree of lipid peroxidation products in the glomeruli. Proteinuria was significantly higher in the diabetic AMKO mice than in the diabetic wild mice. The GC hyperplasia score and the renal prorenin expression were significantly increased in the diabetic AMKO mice than in the diabetic wild mice, and a positive correlation was observed with the NADPH oxidase expression in the macula densa. The endogenous adrenomedullin gene exhibits an antioxidant action via the inhibition of NADPH oxidase probably by suppressing the local renin-angiotensin system.
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spelling doaj-art-e8881d51e73b489dbf231f0f74777be22025-02-03T06:00:46ZengWileyJournal of Diabetes Research2314-67452314-67532013-01-01201310.1155/2013/134395134395The Role of Adrenomedullin in the Renal NADPH Oxidase and (Pro)renin in Diabetic MiceMichio Hayashi0Akihiro Tojo1Tatsuo Shimosawa2Toshiro Fujita3Department of Internal Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, JapanDivision of Nephrology and Endocrinology, Department of Internal Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, JapanDepartment of Internal Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, JapanDepartment of Internal Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, JapanAdrenomedullin has an antioxidative action and protects organs in various diseases. To clarify the role of adrenomedullin in diabetic nephropathy, we investigated the NADPH oxidase expression, renin-secreting granular cell (GC) hyperplasia, and glomerular matrix expansion in the streptozotocin (STZ)-induced diabetic adrenomedullin gene knockout (AMKO) mice compared with the STZ-diabetic wild mice at 10 weeks. The NADPH oxidase p47phox expression and lipid peroxidation products were enhanced in the glomeruli of the diabetic mice compared with that observed in the controls in both wild and AMKO mice. These changes were more obvious in the AMKO mice than in the wild mice. Glomerular mesangial matrix expansion was more severe in the diabetic AMKO mice than in the diabetic wild mice and exhibited a positive correlation with the degree of lipid peroxidation products in the glomeruli. Proteinuria was significantly higher in the diabetic AMKO mice than in the diabetic wild mice. The GC hyperplasia score and the renal prorenin expression were significantly increased in the diabetic AMKO mice than in the diabetic wild mice, and a positive correlation was observed with the NADPH oxidase expression in the macula densa. The endogenous adrenomedullin gene exhibits an antioxidant action via the inhibition of NADPH oxidase probably by suppressing the local renin-angiotensin system.http://dx.doi.org/10.1155/2013/134395
spellingShingle Michio Hayashi
Akihiro Tojo
Tatsuo Shimosawa
Toshiro Fujita
The Role of Adrenomedullin in the Renal NADPH Oxidase and (Pro)renin in Diabetic Mice
Journal of Diabetes Research
title The Role of Adrenomedullin in the Renal NADPH Oxidase and (Pro)renin in Diabetic Mice
title_full The Role of Adrenomedullin in the Renal NADPH Oxidase and (Pro)renin in Diabetic Mice
title_fullStr The Role of Adrenomedullin in the Renal NADPH Oxidase and (Pro)renin in Diabetic Mice
title_full_unstemmed The Role of Adrenomedullin in the Renal NADPH Oxidase and (Pro)renin in Diabetic Mice
title_short The Role of Adrenomedullin in the Renal NADPH Oxidase and (Pro)renin in Diabetic Mice
title_sort role of adrenomedullin in the renal nadph oxidase and pro renin in diabetic mice
url http://dx.doi.org/10.1155/2013/134395
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