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

Jiong Zhang, Norbert Yanez, Anna Floege, Julia Lichtnekert, Ronald D. Krofft, Zhi Hong Liu, Jeffrey W. Pippin, Stuart J. Shankland

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)234-248
Number of pages15
JournalJRAAS - Journal of the Renin-Angiotensin-Aldosterone System
Volume16
Issue number2
DOIs
StatePublished - Jun 15 2015
Externally publishedYes

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Podocytes
Peptidyl-Dipeptidase A
Hydralazine
Enalapril
Focal Segmental Glomerulosclerosis
Epithelial Cells
Blood Pressure
Antibodies
Angiotensin-Converting Enzyme Inhibitors
Drinking Water
Smooth Muscle
Albumins
Creatinine
Histology
Proteins
Theoretical Models
Cell Count
Kidney

Keywords

  • enalapril
  • Focal segmental glomerulosclerosis
  • glomerulosclerosis
  • parietal epithelial cell
  • podocyte
  • regeneration
  • repair

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology

Cite this

ACE-inhibition increases podocyte number in experimental glomerular disease independent of proliferation. / Zhang, Jiong; Yanez, Norbert; Floege, Anna; Lichtnekert, Julia; Krofft, Ronald D.; Liu, Zhi Hong; Pippin, Jeffrey W.; Shankland, Stuart J.

In: JRAAS - Journal of the Renin-Angiotensin-Aldosterone System, Vol. 16, No. 2, 15.06.2015, p. 234-248.

Research output: Contribution to journalArticle

Zhang, Jiong ; Yanez, Norbert ; Floege, Anna ; Lichtnekert, Julia ; Krofft, Ronald D. ; Liu, Zhi Hong ; Pippin, Jeffrey W. ; Shankland, Stuart J. / ACE-inhibition increases podocyte number in experimental glomerular disease independent of proliferation. In: JRAAS - Journal of the Renin-Angiotensin-Aldosterone System. 2015 ; Vol. 16, No. 2. pp. 234-248.
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AU - Liu, Zhi Hong

AU - Pippin, Jeffrey W.

AU - Shankland, Stuart J.

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