Influence of Different Levels of Lipoic Acid Synthase Gene Expression on Diabetic Nephropathy

• Published in: PloS one 2016-10, Vol.11 (10), p.e0163208-e0163208
• Main Authors: Xu, Longquan, Hiller, Sylvia, Simington, Stephen, Nickeleit, Volker, Maeda, Nobuyo, James, Leighton R, Yi, Xianwen
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; Acids; Albumins - analysis; Analysis; Animal models; Animals; Antioxidants; Antioxidants (Nutrients); Biology and Life Sciences; Blood Glucose - analysis; Blood Pressure; Chemokine CCL2 - urine; Clinical trials; Creatinine - urine; Dehydrogenases; Diabetes; Diabetes mellitus; Diabetic nephropathies; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - pathology; Diabetic nephropathy; Disease; Disease Models, Animal; Female; Gene Expression; Genes; Growth factors; Insulin - genetics; Insulin - metabolism; Kidney - pathology; Kidneys; Laboratories; Lipoic acid; Male; Males; Medical research; Medicine; Medicine and Health Sciences; Metabolism; Mice; Mice, Inbred C57BL; Microscopy, Electron; Nephropathy; Oxidative Stress; Pathogenesis; Pathology; Physical Sciences; Proteins; Research and Analysis Methods; Rodents; Sulfurtransferases - genetics; Sulfurtransferases - metabolism; Thickening
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0163208

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.