Influence of Different Levels of Lipoic Acid Synthase Gene Expression on Diabetic Nephropathy.
Oxidative stress is implicated in the pathogenesis of diabetic nephropathy (DN) but outcomes of many clinical trials are controversial. To define the role of antioxidants in kidney protection during the development of diabetic nephropathy, we have generated a novel genetic antioxidant mouse model wi...
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doaj-d87b69de10974cea84f68d7d2f71166d2020-11-24T22:20:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-011110e016320810.1371/journal.pone.0163208Influence of Different Levels of Lipoic Acid Synthase Gene Expression on Diabetic Nephropathy.Longquan XuSylvia HillerStephen SimingtonVolker NickeleitNobuyo MaedaLeighton R JamesXianwen YiOxidative stress is implicated in the pathogenesis of diabetic nephropathy (DN) but outcomes of many clinical trials are controversial. To define the role of antioxidants in kidney protection during the development of diabetic nephropathy, we have generated a novel genetic antioxidant mouse model with over- or under-expression of lipoic acid synthase gene (Lias). These models have been mated with Ins2Akita/+ mice, a type I diabetic mouse model. We compare the major pathologic changes and oxidative stress status in two new strains of the mice with controls. Our results show that Ins2Akita/+ mice with under-expressed Lias gene, exhibit higher oxidative stress and more severe DN features (albuminuria, glomerular basement membrane thickening and mesangial matrix expansion). In contrast, Ins2Akita/+ mice with highly-expressed Lias gene display lower oxidative stress and less DN pathologic changes. Our study demonstrates that strengthening endogenous antioxidant capacity could be an effective strategy for prevention and treatment of DN.http://europepmc.org/articles/PMC5051822?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Longquan Xu Sylvia Hiller Stephen Simington Volker Nickeleit Nobuyo Maeda Leighton R James Xianwen Yi |
spellingShingle |
Longquan Xu Sylvia Hiller Stephen Simington Volker Nickeleit Nobuyo Maeda Leighton R James Xianwen Yi Influence of Different Levels of Lipoic Acid Synthase Gene Expression on Diabetic Nephropathy. PLoS ONE |
author_facet |
Longquan Xu Sylvia Hiller Stephen Simington Volker Nickeleit Nobuyo Maeda Leighton R James Xianwen Yi |
author_sort |
Longquan Xu |
title |
Influence of Different Levels of Lipoic Acid Synthase Gene Expression on Diabetic Nephropathy. |
title_short |
Influence of Different Levels of Lipoic Acid Synthase Gene Expression on Diabetic Nephropathy. |
title_full |
Influence of Different Levels of Lipoic Acid Synthase Gene Expression on Diabetic Nephropathy. |
title_fullStr |
Influence of Different Levels of Lipoic Acid Synthase Gene Expression on Diabetic Nephropathy. |
title_full_unstemmed |
Influence of Different Levels of Lipoic Acid Synthase Gene Expression on Diabetic Nephropathy. |
title_sort |
influence of different levels of lipoic acid synthase gene expression on diabetic nephropathy. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
Oxidative stress is implicated in the pathogenesis of diabetic nephropathy (DN) but outcomes of many clinical trials are controversial. To define the role of antioxidants in kidney protection during the development of diabetic nephropathy, we have generated a novel genetic antioxidant mouse model with over- or under-expression of lipoic acid synthase gene (Lias). These models have been mated with Ins2Akita/+ mice, a type I diabetic mouse model. We compare the major pathologic changes and oxidative stress status in two new strains of the mice with controls. Our results show that Ins2Akita/+ mice with under-expressed Lias gene, exhibit higher oxidative stress and more severe DN features (albuminuria, glomerular basement membrane thickening and mesangial matrix expansion). In contrast, Ins2Akita/+ mice with highly-expressed Lias gene display lower oxidative stress and less DN pathologic changes. Our study demonstrates that strengthening endogenous antioxidant capacity could be an effective strategy for prevention and treatment of DN. |
url |
http://europepmc.org/articles/PMC5051822?pdf=render |
work_keys_str_mv |
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