title: ACE-inhibition increases podocyte number in experimental glomerular disease independent of proliferation.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Nephrology, Department of Medicine, University of Washington School of Medicine, Washington Current address: Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Biostatistics, School of Public Health, University of Washington, Washington.
authors.forename: David
authors.initials: D
authors.lastname: Yanez
authors.affiliation: Division of Nephrology, Department of Medicine, University of Washington School of Medicine, Washington.
authors.forename: Anna
authors.initials: A
authors.lastname: Floege
authors.affiliation: Division of Nephrology, Department of Medicine, University of Washington School of Medicine, Washington.
authors.forename: Julia
authors.initials: J
authors.lastname: Lichtnekert
authors.affiliation: Division of Nephrology, Department of Medicine, University of Washington School of Medicine, Washington.
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Krofft
authors.affiliation: Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, China.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Liu
authors.affiliation: Division of Nephrology, Department of Medicine, University of Washington School of Medicine, Washington.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Pippin
authors.affiliation: Division of Nephrology, Department of Medicine, University of Washington School of Medicine, Washington stuartjs@u.washington.edu.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Shankland
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use; D023381:Endpoint Determination; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D051762:PAX2 Transcription Factor / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D050199:Podocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D011485:Protein Binding / Q000187:drug effects; D012097:Repressor Proteins / Q000378:metabolism; D013599:Systole / Q000187:drug effects; D025721:WT1 Proteins
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000906:Antibodies; D008840:Microfilament Proteins; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; D012097:Repressor Proteins; C503968:Synpo protein, mouse; D025721:WT1 Proteins; C000602896:WT1 protein, mouse; D004656:Enalapril; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Focal segmental glomerulosclerosis; enalapril; glomerulosclerosis; parietal epithelial cell; podocyte; regeneration; repair