title: Activation of the Smad pathway in glomeruli from a spontaneously diabetic rat model, OLETF rats.
abstract: OBJECTIVE
  Transforming growth factor-beta (TGF-beta) mediates the excess accumulation of extracellular matrix in the diabetic kidney. Smad family proteins have been identified as signal transducers for the TGF-beta superfamily. We sought to characterize the role of Smad proteins in mediating TGF-beta responses in the development of diabetic nephropathy.
  
  
  METHODS
  We evaluated the time course of TGF-beta1 fibronectin, Smad2 and Smad3 protein expression and Smad3 activation in glomeruli from spontaneously diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats, using immunohistochemistry and Western blot analysis.
  
  
  RESULTS
  The glomeruli of diabetic OLETF rats showed not only accelerated activation of Smad3, but also enhanced protein expression of Smad2 and Smad3, which occurred in parallel to the increased expression of TGF-beta and fibronectin compared with glomeruli of control, Long-Evans Tokushima Otsuka (LETO) rats at 30 weeks of age. No differences were found in TGF-beta1 fibronectin, Smad2 and Smad3 protein expression and Smad3 activation in glomeruli between the two strains at 12 weeks of age when OLETF rats were not diabetic.
  
  
  CONCLUSIONS
  The enhancement of Smad protein expression and activation may be involved in the TGF-beta signaling cascade that plays an important role in the development of diabetic nephropathy through progressive expansion of the mesangial matrix.
authors.affiliation: Department of Clinical Cell Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Furuse
authors.forename: Naotake
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Mamiko
authors.initials: M
authors.lastname: Maekawa
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Toyama
authors.forename: Atsuhito
authors.initials: A
authors.lastname: Nakao
authors.forename: Itsuo
authors.initials: I
authors.lastname: Iwamoto
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sakurai
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yagui
authors.forename: Shigeki
authors.initials: S
authors.lastname: Yuasa
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Toshimori
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D004195:Disease Models, Animal; D005353:Fibronectins / Q000096:biosynthesis; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D007678:Kidney Glomerulus; D008297:Male; D051381:Rats; D020334:Rats, Inbred OLETF; D015398:Signal Transduction; D051899:Smad2 Protein / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D051900:Smad3 Protein / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology*; D053773:Transforming Growth Factor beta1
chemical_list: D005353:Fibronectins; D051899:Smad2 Protein; D051900:Smad3 Protein; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1