title: Reciprocal balance of hepatocyte growth factor and transforming growth factor-beta 1 in renal fibrosis in mice.
abstract: BACKGROUND
  Transforming growth factor-beta 1 (TGF-beta 1) plays a central role in the pathogenesis of renal fibrosis. In contrast, hepatocyte growth factor (HGF) may be an important molecule for tissue repair. As TGF-beta 1 is a suppressor molecule for HGF expression, we asked whether a decrease in HGF expression would be accompanied by an increase in TGF-beta 1 and whether the progression of renal fibrosis would be modulated.
  
  
  METHODS
  We used the ICR strain-derived glomerulonephritis (ICGN) mice as a model of chronic renal disease and examined changes in local HGF expression during the natural course of renal fibrosis. To determine the significance of intrinsic HGF noted during progression of renal fibrosis, we administered an anti-HGF antibody to mice at the early stage of renal fibrosis.
  
  
  RESULTS
  At an early stage of renal fibrosis, the mice showed strong peritubular HGF expression, coinciding with tubular proliferation. In the late stages, the renal HGF level was markedly decreased, coinciding with a reduction in proliferative tubular areas. Renal TGF-beta 1 levels were increased in accordance with expansion of fibrotic areas. Notably, the anti-HGF antibody treatment of early-stage mice decreased the HGF level and reduced tubular areas, whereas collagen-deposited areas were expanded in parallel with increased TGF-beta 1 levels. Consequently, in HGF-neutralized mice, there was a rapid progression of renal dysfunction.
  
  
  CONCLUSIONS
  Not only an increase in TGF-beta 1 level, but also a decrease in local HGF expression may be responsible for the manifestation of renal fibrosis, particularly tubular destruction.
authors.affiliation: Department of Oncology, Biomedical Research Center, Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Mizuno
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: T
authors.initials: T
authors.lastname: Kurosawa
authors.forename: Y
authors.initials: Y
authors.lastname: Mizuno-Horikawa
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005921:Glomerulonephritis / Q000378:metabolism / Q000473:pathology; D017228:Hepatocyte Growth Factor / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D007684:Kidney Tubules / Q000473:pathology; D051379:Mice; D010641:Phenotype; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D007074:Immunoglobulin G; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D017228:Hepatocyte Growth Factor