Podocyte-specific overexpression of human angiotensin-converting enzyme 2 attenuates diabetic nephropathy in mice
Description
Title: | Podocyte-specific overexpression of human angiotensin-converting enzyme 2 attenuates diabetic nephropathy in mice |
Authors: | Nadarajah, Renisha Milagres, Rosangela Dilauro, Marc Gutsol, Alex Xiao, Fengxia Zimpelmann, Joseph Kennedy, Chris Wysocki, Jan Batlle, Daniel Burns, Kevin D. |
Date: | 2012-08-24 |
Abstract: | Angiotensin-converting enzyme 2 (ACE2) degrades angiotensin II to angiotensin-(1–7) and is expressed in podocytes. Here we overexpressed ACE2 in podocytes in experimental diabetic nephropathy using transgenic methods where a nephrin promoter drove the expression of human ACE2. Glomeruli from these mice had significantly increased mRNA, protein, and activity of ACE2 compared to wild-type mice. Male mice were treated with streptozotocin to induce diabetes. After 16 weeks, there was no significant difference in plasma glucose levels between wild-type and transgenic diabetic mice. Urinary albumin was significantly increased in wild-type diabetic mice at 4 weeks, whereas albuminuria in transgenic diabetic mice did not differ from wild-type nondiabetic mice. However, this effect was transient and by 16 weeks both transgenic and nontransgenic diabetic mice had similar rates of proteinuria. Compared to wild-type diabetic mice, transgenic diabetic mice had an attenuated increase in mesangial area, decreased glomerular area, and a blunted decrease in nephrin expression. Podocyte numbers decreased in wild-type diabetic mice at 16 weeks, but were unaffected in transgenic diabetic mice. At 8 weeks, kidney cortical expression of transforming growth factor-β1 was significantly inhibited in transgenic diabetic mice as compared to wild-type diabetic mice. Thus, the podocyte-specific overexpression of human ACE2 transiently attenuates the development of diabetic nephropathy. |
URL: | http://hdl.handle.net/10393/23202 |
DOI: | 10.1038/ki.2012.83 |
Collection | Médecine // Medicine Publications en libre accès financées par uOttawa // uOttawa financed open access publications |
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Nadarajah_Renisha_2012_Podocyte-specific_overexpression.pdf | 1.12 MB | Adobe PDF | Open |