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ACE-inhibition increases podocyte number in experimental glomerular disease independent of proliferation.

Publication ,  Journal Article
Zhang, J; Yanez, D; Floege, A; Lichtnekert, J; Krofft, RD; Liu, Z-H; Pippin, JW; Shankland, SJ
Published in: J Renin Angiotensin Aldosterone Syst
June 2015

OBJECTIVE: The objective of this article is to test the effects of angiotensin-converting enzyme (ACE)-inhibition on glomerular epithelial cell number in an inducible experimental model of focal segmental glomerulosclerosis (FSGS). BACKGROUND: Although ACE-inhibition has been shown to limit podocyte loss by enhancing survival, little is known about its effect on podocyte number following an abrupt decline in disease. METHODS: Experimental FSGS was induced with cytotoxic antipodocyte antibody. Following induction, groups were randomized to receive the ACE-inhibitor enalapril, the smooth muscle relaxant hydralazine (blood pressure control) or drinking water. Blood pressure, kidney function and histology were measured seven and 14 days following disease induction. RESULTS: Both glomerulosclerosis and urinary albumin-to-creatinine ratio were less in the ACE-inhibition arm at day 14. At day 7 of disease, mean podocyte numbers were 26% and 29% lower in the enalapril and hydralazine arms, respectively, compared to normal mice in which no antibody was injected. At day 14, the mean podocyte number was only 18% lower in the enalapril arm, but was 39% lower in the hydralazine arm compared to normal mice. Podocyte proliferation did not occur at any time in any group. Compared to water- or hydralazine-treated mice with FSGS, the enalapril arm had a higher mean number of glomerular parietal epithelial cells that co-expressed the podocyte proteins WT-1 and synaptopodin, as well as phospho-ERK. CONCLUSION: The results show following an abrupt decline in podocyte number, the initiation of ACE-inhibition but not hydralazine, was accompanied by higher podocyte number in the absence of proliferation. This was accompanied by a higher number of parietal epithelial cells that co-express podocyte proteins. Increasing podocyte number appears to be accompanied by reduced glomerulosclerosis.

Duke Scholars

Published In

J Renin Angiotensin Aldosterone Syst

DOI

EISSN

1752-8976

Publication Date

June 2015

Volume

16

Issue

2

Start / End Page

234 / 248

Location

England

Related Subject Headings

  • WT1 Proteins
  • Systole
  • Repressor Proteins
  • Protein Binding
  • Podocytes
  • Phosphorylation
  • PAX2 Transcription Factor
  • Microfilament Proteins
  • Mice
  • Glomerulosclerosis, Focal Segmental
 

Citation

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Zhang, J., Yanez, D., Floege, A., Lichtnekert, J., Krofft, R. D., Liu, Z.-H., … Shankland, S. J. (2015). ACE-inhibition increases podocyte number in experimental glomerular disease independent of proliferation. J Renin Angiotensin Aldosterone Syst, 16(2), 234–248. https://doi.org/10.1177/1470320314543910
Zhang, Jiong, David Yanez, Anna Floege, Julia Lichtnekert, Ronald D. Krofft, Zhi-Hong Liu, Jeffrey W. Pippin, and Stuart J. Shankland. “ACE-inhibition increases podocyte number in experimental glomerular disease independent of proliferation.J Renin Angiotensin Aldosterone Syst 16, no. 2 (June 2015): 234–48. https://doi.org/10.1177/1470320314543910.
Zhang J, Yanez D, Floege A, Lichtnekert J, Krofft RD, Liu Z-H, et al. ACE-inhibition increases podocyte number in experimental glomerular disease independent of proliferation. J Renin Angiotensin Aldosterone Syst. 2015 Jun;16(2):234–48.
Zhang, Jiong, et al. “ACE-inhibition increases podocyte number in experimental glomerular disease independent of proliferation.J Renin Angiotensin Aldosterone Syst, vol. 16, no. 2, June 2015, pp. 234–48. Pubmed, doi:10.1177/1470320314543910.
Zhang J, Yanez D, Floege A, Lichtnekert J, Krofft RD, Liu Z-H, Pippin JW, Shankland SJ. ACE-inhibition increases podocyte number in experimental glomerular disease independent of proliferation. J Renin Angiotensin Aldosterone Syst. 2015 Jun;16(2):234–248.

Published In

J Renin Angiotensin Aldosterone Syst

DOI

EISSN

1752-8976

Publication Date

June 2015

Volume

16

Issue

2

Start / End Page

234 / 248

Location

England

Related Subject Headings

  • WT1 Proteins
  • Systole
  • Repressor Proteins
  • Protein Binding
  • Podocytes
  • Phosphorylation
  • PAX2 Transcription Factor
  • Microfilament Proteins
  • Mice
  • Glomerulosclerosis, Focal Segmental