title: Effect of Heme Oxygenase-1 Deficiency on Glomerular Proteomics.
abstract: The cytoprotective effect of heme oxygenase (HO)-1 in various forms of renal glomerular injury is established. However, little is known on the role of HO-1 in preserving glomerular structural/functional integrity in the absence of injury. The present study addressed this question in HO-1-deficient rats.
  
  
  
  HO-1-deficient rats were generated using zinc finger nuclease-mediated HO-1 gene (Hmox1) disruption and studied. Glomeruli were isolated from HO-1-deficient (Hmox1-/-) rats and their wild type (WT) littermates for proteomic analysis.
  
  
  
  Glomerular lesions were characterized and differentially expressed proteins important for preserving integrity of the glomerular filtration barrier were identified. HO-1-deficient (Hmox1-/-) rats developed albuminuria with decreased glomerular filtration rate. In albuminuric rats, there were lesions resembling focal and segmental glomerulosclerosis (FSGS). Western blot analysis of the integral slit diaphragm proteins, nephrin and podocin revealed a significant decrease in nephrin, with no change in podocin. Proteomic analysis of glomerular protein lysates from Hmox1-/- and WT rats revealed differential expression of proteins previously linked with FSGS pathogenesis. Specifically, α-actinin-4, actin related protein 3, cytokeratins and novel candidates including transgelin-2 and lamins. Bioinformatic analysis predicted the upregulation of pathways implicated in platelet aggregation and fibrin clot formation.
  
  
  
  HO-1 is a putative regulator of proteins important in preserving glomerular structural stability and integrity, and in minimizing the activity of proinflammatory pathways.
authors.affiliation: Department of Critical Care Medicine and Pulmonary Services, University of Athens School of Medicine, Athens, Greece.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Detsika
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Lygirou
authors.forename: Vassileios
authors.initials: V
authors.lastname: Frantzis
authors.forename: Jerome
authors.initials: J
authors.lastname: Zoidakis
authors.forename: Vassilios
authors.initials: V
authors.lastname: Atsaves
authors.forename: Elpida
authors.initials: E
authors.lastname: Poulaki
authors.forename: Hariklia
authors.initials: H
authors.lastname: Gakiopoulou
authors.forename: Antonia
authors.initials: A
authors.lastname: Vlahou
authors.forename: Elias A
authors.initials: EA
authors.lastname: Lianos
mesh_terms: D000743:Anemia, Hemolytic / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D006130:Growth Disorders / Q000378:metabolism* / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000172:deficiency* / Q000378:metabolism; D019189:Iron Metabolism Disorders / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020543:Proteome; D017207:Rats, Sprague-Dawley
chemical_list: D020543:Proteome; D051547:Heme Oxygenase-1