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

Kidney Int. 2012 Aug;82(3):292-303. doi: 10.1038/ki.2012.83. Epub 2012 Apr 4.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Blood Pressure
  • Diabetic Nephropathies / enzymology*
  • Diabetic Nephropathies / genetics*
  • Diabetic Nephropathies / pathology
  • Diabetic Nephropathies / physiopathology
  • Glomerular Filtration Rate
  • Glomerular Mesangium / enzymology
  • Glomerular Mesangium / pathology
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Peptidyl-Dipeptidase A / genetics*
  • Peptidyl-Dipeptidase A / metabolism*
  • Podocytes / enzymology*
  • Podocytes / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Transforming Growth Factor beta1 / metabolism
  • Up-Regulation


  • RNA, Messenger
  • Recombinant Proteins
  • Transforming Growth Factor beta1
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2