Zhang, JiongYanez, DavidFloege, AnnaLichtnekert, JuliaKrofft, Ronald DLiu, Zhi-HongPippin, Jeffrey WShankland, Stuart J2023-01-252023-01-252015-061470-32031752-8976https://hdl.handle.net/10161/26502<h4>Objective</h4>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).<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.Epithelial CellsAnimalsMiceMicrofilament ProteinsExtracellular Signal-Regulated MAP KinasesEnalaprilWT1 ProteinsRepressor ProteinsAntibodiesAngiotensin-Converting Enzyme InhibitorsEndpoint DeterminationCell CountCell ProliferationProtein BindingPhosphorylationBlood PressureSystolePodocytesPAX2 Transcription FactorGlomerulosclerosis, Focal SegmentalJournal article2023-01-25