title: Superoxide overproduction and kidney fibrosis: a new animal model.
abstract: OBJECTIVE
  To establish whether the mutation in the Immp2L gene induces renal fibrosis and whether aging exacerbates renal morphology in mice.
  
  
  METHODS
  Female mutant mice with mutation in the inner mitochondrial membrane peptidase 2-like protein at 3 and 18 months of age were used. Renal fibrosis was analyzed using classic fibrosis score, Masson's trichrome staining, and analysis of profibrotic markers using real time polymerase chain reaction (superoxide dismutase 1, metalloproteinase-9, erythropoietin, transforming growth factor beta), and immunostaining (fibroblasts and Type IV collagen). Oxidative stress markers were determined by immunohistochemistry. The number of renal apoptotic cells was determined. Renal function was estimated by serum creatinine.
  
  
  RESULTS
  Young mutant mice had significantly more glomerulosclerosis than age-matched mice (p=0.034). Mutant mice had more tubular casts (p=0.025), collagen deposition (p=0.019), and collagen type IV expression (p<0.001). Superoxide dismutase 1 expression was significantly higher in young mutants (p=0.038). Old mutants exhibited significantly higher expression of the fibroblast marker and macrophage marker (p=0.007 and p=0.012, respectively). The real time polymerase chain reaction of metalloproteinase-9 and erythropoietin were enhanced 2.5- and 6-fold, respectively, in old mutants. Serum creatinine was significantly higher in old mutants (p<0.001).
  
  
  CONCLUSIONS
  This mutation altered renal architecture by increasing the deposition of extracellular matrix, oxidative stress, and inflammation, suggesting a protective role of Immp2L against renal fibrosis.
authors.affiliation: Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
authors.forename: Nadia Karina
authors.initials: NK
authors.lastname: Guimarães-Souza
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA.
authors.forename: Liliya Marsovna
authors.initials: LM
authors.lastname: Yamaleyeva
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA.
authors.forename: Baisong
authors.initials: B
authors.lastname: Lu
authors.affiliation: Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
authors.forename: Ana Claudia Mallet de Souza
authors.initials: AC
authors.lastname: Ramos
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA.
authors.forename: Colin Edward
authors.initials: CE
authors.lastname: Bishop
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA.
authors.forename: Karl Erik
authors.initials: KE
authors.lastname: Andersson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D003094:Collagen / Q000032:analysis; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism*; D004921:Erythropoietin / Q000032:analysis; D005260:Female; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D051379:Mice; D009154:Mutation / Q000502:physiology*; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D051436:Renal Insufficiency, Chronic / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000032:analysis; D000072105:Superoxide Dismutase-1; D013481:Superoxides / Q000032:analysis / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000032:analysis
chemical_list: C000606290:SOD1 protein, human; D016212:Transforming Growth Factor beta; D013481:Superoxides; D004921:Erythropoietin; D003094:Collagen; D003404:Creatinine; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D010450:Endopeptidases; C425070:IMMP2L protein, human; D020780:Matrix Metalloproteinase 9