Open AccessInfluence of Different Levels of Lipoic Acid Synthase Gene Expression on Diabetic Nephropathy
Author(s) -
Lan Xu,
Sylvia Hiller,
Stephen Simington,
Volker Nickeleit,
Nobuyo Maeda,
Leighton R. James,
Xin Yi
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0163208
Subject(s) - diabetic nephropathy , oxidative stress , glomerular basement membrane , albuminuria , endocrinology , gene expression , medicine , lipoic acid , nephropathy , biology , antioxidant , diabetes mellitus , kidney , gene , biochemistry , glomerulonephritis
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 Ins2 Akita/+ 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 Ins2 Akita/+ 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, Ins2 Akita/+ 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.