title: Attenuation of interstitial fibrosis and tubular apoptosis in db/db transgenic mice overexpressing catalase in renal proximal tubular cells.
abstract: OBJECTIVE
  The present study investigated the relationships between reactive oxygen species (ROS), interstitial fibrosis, and renal proximal tubular cell (RPTC) apoptosis in type 2 diabetic db/db mice and in db/db transgenic (Tg) mice overexpressing rat catalase (rCAT) in their RPTCs (db/db rCAT-Tg).
  
  
  METHODS
  Blood pressure, blood glucose, and albuminuria were monitored for up to 5 months. Kidneys were processed for histology and apoptosis studies (terminal transferase-mediated dUTP nick-end labeling or immunostaining for active caspase-3 and Bax). Real-time quantitative PCR assays were used to quantify angiotensinogen (ANG), p53, and Bax mRNA levels.
  
  
  RESULTS
  db/db mice developed obesity, hyperglycemia, hypertension, and albuminuria. In contrast, db/db rCAT-Tg mice became obese and hyperglycemic but had normal blood pressure and attenuated albuminuria compared with db/db mice. Kidneys from db/db mice displayed progressive glomerular hypertrophy, glomerulosclerosis, interstitial fibrosis, and tubular apoptosis and increased expression of collagen type IV, Bax, and active caspase-3, as well as increased ROS production. These changes, except glomerular hypertrophy, were markedly attenuated in kidneys of db/db rCAT-Tg mice. Furthermore, ANG, p53, and Bax mRNA expression was increased in renal proximal tubules of db/db mice but not of db/db rCAT-Tg mice.
  
  
  CONCLUSIONS
  Our results indicate a crucial role for intra-renal ROS in the progression of hypertension, albuminuria, interstitial fibrosis, and tubular apoptosis in type 2 diabetes and demonstrate the beneficial effects of suppressing ROS formation.
authors.affiliation: Université de Montréal, Centre hospitalier de l'Université de Montréal (CHUM) Hôtel-Dieu, Research Centre, Pavillon Masson, 3850 Saint Urbain St., Montreal, Quebec, Canada.
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Brezniceanu
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Chih-Chang
authors.initials: CC
authors.lastname: Wei
authors.forename: Isabelle
authors.initials: I
authors.lastname: Chénier
authors.forename: Nicolas
authors.initials: N
authors.lastname: Godin
authors.forename: Shao-Ling
authors.initials: SL
authors.lastname: Zhang
authors.forename: Janos G
authors.initials: JG
authors.lastname: Filep
authors.forename: Julie R
authors.initials: JR
authors.lastname: Ingelfinger
authors.forename: John S D
authors.initials: JS
authors.lastname: Chan
mesh_terms: D000818:Animals; D017209:Apoptosis; D002374:Catalase / Q000235:genetics* / Q000378:metabolism; D002417:Cattle; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology*; D003928:Diabetic Nephropathies; D020287:In Situ Nick-End Labeling; D007687:Kidney Tubules, Proximal / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009395:Nephritis, Interstitial / Q000201:enzymology / Q000235:genetics*; D009765:Obesity / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D002374:Catalase