Hmox1 Deficiency Sensitizes Mice to Peroxynitrite Formation and Diabetic Glomerular Microvascular Injuries
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...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2017/9603924 |
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| author | Olivia Lenoir François Gaillard Hélène Lazareth Blaise Robin Pierre-Louis Tharaux |
| author_facet | Olivia Lenoir François Gaillard Hélène Lazareth Blaise Robin Pierre-Louis Tharaux |
| author_sort | Olivia Lenoir |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ca73b2bd71db4813a6e82bd8308c9721 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-ca73b2bd71db4813a6e82bd8308c97212025-02-03T01:12:59ZengWileyJournal of Diabetes Research2314-67452314-67532017-01-01201710.1155/2017/96039249603924Hmox1 Deficiency Sensitizes Mice to Peroxynitrite Formation and Diabetic Glomerular Microvascular InjuriesOlivia Lenoir0François Gaillard1Hélène Lazareth2Blaise Robin3Pierre-Louis Tharaux4Paris Cardiovascular Centre (PARCC), Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, FranceParis Cardiovascular Centre (PARCC), Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, FranceParis Cardiovascular Centre (PARCC), Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, FranceParis Cardiovascular Centre (PARCC), Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, FranceParis Cardiovascular Centre (PARCC), Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, FranceObjective. 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.http://dx.doi.org/10.1155/2017/9603924 |
| spellingShingle | Olivia Lenoir François Gaillard Hélène Lazareth Blaise Robin Pierre-Louis Tharaux Hmox1 Deficiency Sensitizes Mice to Peroxynitrite Formation and Diabetic Glomerular Microvascular Injuries Journal of Diabetes Research |
| title | Hmox1 Deficiency Sensitizes Mice to Peroxynitrite Formation and Diabetic Glomerular Microvascular Injuries |
| title_full | Hmox1 Deficiency Sensitizes Mice to Peroxynitrite Formation and Diabetic Glomerular Microvascular Injuries |
| title_fullStr | Hmox1 Deficiency Sensitizes Mice to Peroxynitrite Formation and Diabetic Glomerular Microvascular Injuries |
| title_full_unstemmed | Hmox1 Deficiency Sensitizes Mice to Peroxynitrite Formation and Diabetic Glomerular Microvascular Injuries |
| title_short | Hmox1 Deficiency Sensitizes Mice to Peroxynitrite Formation and Diabetic Glomerular Microvascular Injuries |
| title_sort | hmox1 deficiency sensitizes mice to peroxynitrite formation and diabetic glomerular microvascular injuries |
| url | http://dx.doi.org/10.1155/2017/9603924 |
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