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Journal of Diabetes Research
Volume 2017 (2017), Article ID 9603924, 7 pages
https://doi.org/10.1155/2017/9603924
Research Article

Hmox1 Deficiency Sensitizes Mice to Peroxynitrite Formation and Diabetic Glomerular Microvascular Injuries

1Paris Cardiovascular Centre (PARCC), Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France
2Université Paris Descartes, Sorbonne Paris Cité, Paris, France
3Nephrology Division, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France

Correspondence should be addressed to Olivia Lenoir and Pierre-Louis Tharaux

Received 10 May 2017; Revised 6 September 2017; Accepted 8 October 2017; Published 22 November 2017

Academic Editor: Hiroshi Okamoto

Copyright © 2017 Olivia Lenoir et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective. Indirect evidence suggests a role for heme oxygenase-1 (HO-1) in limiting diabetic vasculopathy. The goal of this study was to assess the role of HO-1 in the development of microvascular lesions within glomeruli during diabetes mellitus using a mouse model with specific alteration of the Hmox1 gene. Approach and Results. The effects of Hmox1 haploinsufficiency were studied as a means of assessing the intrinsic contribution of HO-1 in the development of renal microvascular lesions during diabetes. Renal function and histology were analyzed 10 weeks after diabetes induction with streptozotocin. Diabetic Hmox1+/− mice showed higher levels of albuminuria and blood urea compared to their wild-type diabetic littermates. More severe glomerular microvascular lesions were also observed in the diabetic Hmox1+/− mice. This was associated with a renal increase in the expression of the oxidative stress marker, nitrotyrosine. Conclusions. Genetic Hmox1 partial deficiency is sufficient to sensitize mice to the development of diabetic glomerular microvascular lesions. HO-1 exerts antioxidant effects in the kidney during diabetes mellitus. These have protective effects on the development of glomerular endothelial injury.