title: Glomerular Epithelial Cells-Targeted Heme Oxygenase-1 Over Expression in the Rat: Attenuation of Proteinuria in Secondary But Not Primary Injury.
abstract: OBJECTIVE
  Induction of heme oxygenase 1 (HO-1) in glomerular epithelial cells (GEC) in response to injury is poor and this may be a disadvantage. We, therefore, explored whether HO-1 overexpression in GEC can reduce proteinuria induced by puromycin aminonucleoside (PAN) or in anti-glomerular basement membrane (GBM) antibody (Ab)-mediated glomerulonephritis (GN).
  
  
  METHODS
  HO-1 overexpression in GEC (GECHO-1) of Sprague-Dawley rats was achieved by targeting a FLAG-human (h) HO-1 using transposon-mediated transgenesis. Direct GEC injury was induced by a single injection of PAN. GN was induced by administration of an anti-rat GBM Ab and macrophage infiltration in glomeruli was assessed by immunohistochemistry and western blot analysis, which was also used to assess glomerular nephrin expression.
  
  
  RESULTS
  In GECHO-1 rats, FLAG-hHO-1 transprotein was co-immunolocalized with nephrin. Baseline glomerular HO-1 protein levels were higher in GECHO-1 compared to wild type (WT) rats. Administration of either PAN or anti-GBM Ab to WT rats increased glomerular HO-1 levels. Nephrin expression markedly decreased in glomeruli of WT or GECHO-1 rats treated with PAN. In anti-GBM Ab-treated WT rats, nephrin expression also decreased. In contrast, it was preserved in anti-GBM Ab-treated GECHO-1 rats. In these, macrophage infiltration in glomeruli and the ratio of urine albumin to urine creatinine (Ualb/Ucreat) were markedly reduced. There was no difference in Ualb/Ucreat between WT and GECHO-1 rats treated with PAN.
  
  
  CONCLUSIONS
  Depending on the type of injury, HO-1 overexpression in GEC may or may not reduce proteinuria. Reduced macrophage infiltration and preservation of nephrin expression are putative mechanisms underlying the protective effect of HO-1 overexpression following immune injury.
authors.affiliation: Department of Medicine, Division of Critical Care Medicine and Pulmonary Services, University of Athens School of Health Sciences, Athens, Greece.
authors.forename: Vassilios
authors.initials: V
authors.lastname: Atsaves
authors.forename: Panagiota
authors.initials: P
authors.lastname: Makri
authors.forename: Maria G
authors.initials: MG
authors.lastname: Detsika
authors.forename: Alexandra
authors.initials: A
authors.lastname: Tsirogianni
authors.forename: Elias A
authors.initials: EA
authors.lastname: Lianos
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000166:cytology* / Q000201:enzymology; D011507:Proteinuria / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic
chemical_list: D051547:Heme Oxygenase-1