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

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...

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Detalles Bibliográficos
Autores principales: Zhang, Jiong, Yanez, David, Floege, Anna, Lichtnekert, Julia, Krofft, Ronald D, Liu, Zhi-Hong, Pippin, Jeffrey W, Shankland, Stuart J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412792/
https://www.ncbi.nlm.nih.gov/pubmed/25143333
http://dx.doi.org/10.1177/1470320314543910
Descripción
Sumario: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.