title: Influence of Different Levels of Lipoic Acid Synthase Gene Expression on Diabetic Nephropathy.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Longquan
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Hiller
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Stephen
authors.initials: S
authors.lastname: Simington
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Volker
authors.initials: V
authors.lastname: Nickeleit
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Nobuyo
authors.initials: N
authors.lastname: Maeda
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, University of Florida, Jacksonville, Florida, United States of America.
authors.forename: Leighton R
authors.initials: LR
authors.lastname: James
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Xianwen
authors.initials: X
authors.lastname: Yi
mesh_terms: D020413:3' Untranslated Regions; D000418:Albumins / Q000032:analysis; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D018932:Chemokine CCL2 / Q000652:urine; D003404:Creatinine / Q000652:urine; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D018384:Oxidative Stress; D013466:Sulfurtransferases / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D000418:Albumins; D001786:Blood Glucose; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C561967:Ins2 protein, mouse; D007328:Insulin; D003404:Creatinine; D013466:Sulfurtransferases; C116435:lipoic acid synthase