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

dc.contributor.author

Zhang, Jiong

dc.contributor.author

Yanez, David

dc.contributor.author

Floege, Anna

dc.contributor.author

Lichtnekert, Julia

dc.contributor.author

Krofft, Ronald D

dc.contributor.author

Liu, Zhi-Hong

dc.contributor.author

Pippin, Jeffrey W

dc.contributor.author

Shankland, Stuart J

dc.date.accessioned

2023-01-25T21:40:27Z

dc.date.available

2023-01-25T21:40:27Z

dc.date.issued

2015-06

dc.date.updated

2023-01-25T21:40:25Z

dc.description.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.
dc.identifier

1470320314543910

dc.identifier.issn

1470-3203

dc.identifier.issn

1752-8976

dc.identifier.uri

https://hdl.handle.net/10161/26502

dc.language

eng

dc.publisher

Hindawi Limited

dc.relation.ispartof

Journal of the renin-angiotensin-aldosterone system : JRAAS

dc.relation.isversionof

10.1177/1470320314543910

dc.subject

Epithelial Cells

dc.subject

Animals

dc.subject

Mice

dc.subject

Microfilament Proteins

dc.subject

Extracellular Signal-Regulated MAP Kinases

dc.subject

Enalapril

dc.subject

WT1 Proteins

dc.subject

Repressor Proteins

dc.subject

Antibodies

dc.subject

Angiotensin-Converting Enzyme Inhibitors

dc.subject

Endpoint Determination

dc.subject

Cell Count

dc.subject

Cell Proliferation

dc.subject

Protein Binding

dc.subject

Phosphorylation

dc.subject

Blood Pressure

dc.subject

Systole

dc.subject

Podocytes

dc.subject

PAX2 Transcription Factor

dc.subject

Glomerulosclerosis, Focal Segmental

dc.title

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

dc.type

Journal article

duke.contributor.orcid

Yanez, David|0000-0002-2501-5028

pubs.begin-page

234

pubs.end-page

248

pubs.issue

2

pubs.organisational-group

Duke

pubs.organisational-group

School of Medicine

pubs.organisational-group

Basic Science Departments

pubs.organisational-group

Biostatistics & Bioinformatics

pubs.publication-status

Published

pubs.volume

16

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