Podocyte-specific overexpression of human angiotensin-converting enzyme 2 attenuates diabetic nephropathy in mice

FieldValue
dc.contributor.authorNadarajah, Renisha
dc.contributor.authorMilagres, Rosangela
dc.contributor.authorDilauro, Marc
dc.contributor.authorGutsol, Alex
dc.contributor.authorXiao, Fengxia
dc.contributor.authorZimpelmann, Joseph
dc.contributor.authorKennedy, Chris
dc.contributor.authorWysocki, Jan
dc.contributor.authorBatlle, Daniel
dc.contributor.authorBurns, Kevin D.
dc.date.accessioned2012-08-24T14:32:18Z
dc.date.available2012-08-24T14:32:18Z
dc.date.created2012
dc.date.issued2012-08-24
dc.identifier.urihttp://hdl.handle.net/10393/23202
dc.description.abstractAngiotensin-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.
dc.language.isoen
dc.subjectACE2
dc.subjectalbuminuria
dc.subjectangiotensin
dc.subjectapoptosis
dc.subjectdiabetes
dc.subjectpodocyte
dc.titlePodocyte-specific overexpression of human angiotensin-converting enzyme 2 attenuates diabetic nephropathy in mice
dc.typeArticle
dc.identifier.doi10.1038/ki.2012.83
CollectionMédecine // Medicine
Publications en libre accès financées par uOttawa // uOttawa financed open access publications

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