title: Hepatocyte growth factor gene therapy slows down the progression of diabetic nephropathy in db/db mice.
abstract: BACKGROUND
  Effect of hepatocyte growth factor (HGF) has scarcely been determined on diabetic nephropathy.
  
  
  METHODS
  Adenovirus encoding human HGF gene or LacZ gene (as the control) was injected into the hindlimb muscles of the C57BL/KsJ-db/db (db/db) mice at the age of 12 weeks, a model of genetic diabetes. Diabetic nephropathy was then evaluated at the age of 24 weeks.
  
  
  RESULTS
  The urine volume and albumin excretion progressively decreased in the control, whereas they remained unchanged in the HGF-treated group during the 12-week follow-up. The HGF gene therapy did not affect glucose metabolism. However, it resulted in a better renal function as evaluated by creatinine clearance (Ccr) than the control; Ccr was progressively worsened in controls (0.14 +/- 0.02 liters/day) whereas unchanged in the HGF gene-treated group (0.38 +/- 0.09 liters/day, p < 0.05). Kidneys of the HGF gene-treated mice showed glomeruli with greater area and cell population, smaller glomerular sclerotic index, and less fibrosis in both glomeruli and renal tubules, where apoptotic rate of glomerular endothelial cells and that of tubular epithelial cells were significantly decreased. TGF-beta1 expression was significantly decreased in kidneys of the HGF gene-treated group. Finally, the HGF treatment significantly improved the long-term survival of db/db mice.
  
  
  CONCLUSIONS
  The HGF gene delivery thus appeared to slow down the aggravation of diabetic nephropathy in db/db mice by attenuating progression from the hyperfiltration phase into the sclerotic phase through antiapoptotic and antifibrotic actions. The present findings suggest that the HGF gene delivery can be a novel therapeutic approach against diabetic nephropathy.
authors.affiliation: Department of Internal Medicine, Gifu University School of Medicine, Gifu, Japan.
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Kagawa
authors.forename: Genzou
authors.initials: G
authors.lastname: Takemura
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Kosai
authors.forename: Ichijiro
authors.initials: I
authors.lastname: Murata
authors.forename: Takamasa
authors.initials: T
authors.lastname: Ohno
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Masayasu
authors.initials: M
authors.lastname: Esaki
authors.forename: Rumi
authors.initials: R
authors.lastname: Maruyama
authors.forename: Takako
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Ohashi
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Fujiwara
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D004279:DNA, Viral / Q000008:administration & dosage; D003928:Diabetic Nephropathies / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000627:therapeutic use*; D006801:Humans; D007677:Kidney Function Tests; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000235:genetics / Q000627:therapeutic use; D012720:Severity of Illness Index; D014162:Transfection / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D004279:DNA, Viral; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor