NADPH-OXIDASE NOX5 AGGRAVATES RENAL INJURY IN THE AKITA MOUSE MODEL OF DIABETIC NEPHROPATHY

J JHA1, R TOUYZ2, C KENNEDY3, M COOPER1, K JANDELEIT-DAHM1
1Department Of Diabetes, Melbourne, Australia, 2Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom, 3Department of Medicine, Ottawa Hospital Research Institute, Ottawa, Canada

Background: Renal reactive oxygen species (ROS) play an important role in mediating kidney injury in diabetes. Increasing evidence suggests that the pro-oxidant enzyme, Nox5 plays a significant role in human diabetic nephropathy (DN). Nox5 is present in humans and rabbits but not in mice or rats. Thus, there is a paucity of information about Nox5 in conventional animal models of DN. We examined the role of Nox5 in the insulin deficient diabetic Akita mice model using human inducible transgenic mice that express Nox5 selectively in endothelial cells (VEcad+Nox5+) or in mesangial cells (SM22+Nox5+).
Methods: At week 10 mice were culled and kidneys were removed for the assessment of structural damage as well as gene and protein expression of markers of inflammation, fibrosis and oxidative stress. Protein expression of Nox5 and its localization in glomerular cells (endothelial and mesangial cells) were examined in transgenic mice by immunostaining.
Results: Expression of Nox5 was confirmed in glomerular endothelial and mesangial cells of transgenic mice. Diabetes induced increase in glomerulosclerosis, gene and protein expression of fibronectin and MCP-1 as well as nitrotyrosine were further increase in both diabetic Nox5 transgenic mice.
Conclusions: These findings suggest that Nox5 expression in endothelial or mesangial cells in an streptozotocin independent model of type 1 diabetes is associated with increased ROS production and accelerates renal injury in diabetes.


Biography:
Prof Jandeleit-Dahm is a physician scientist  and nephrologist. Her main research focus is the role of reactive oxygen species in the kidney and in cardiovascular complications of diabetes.

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