title: Effect of Smad pathway activation on podocyte cell cycle regulation: an immunohistochemical evaluation.
abstract: BACKGROUND
  Mature podocytes are in cell cycle arrest and their inability to proliferate successfully is a consequence of negative cell-cycle regulators' expression, such as p57. Phosphorylated smad2/smad3 (pSmad2/3) is an intracellular heteromeric mediator of transforming growth factor beta (TGF-β) signals and, together with co-activators such as P300, regulates gene transcription, including cell cycle regulator proteins.
  
  
  METHODS
  In order to investigate Smad pathway activation and podocyte cell cycle regulation in glomerular injury, we studied the glomerular immunohistochemical expression of p57, pSmad2/3 and P300 in samples from 67 patients with various types of glomerulonephritis (GN) and 10 normal kidney tissue specimens.
  
  
  RESULTS
  pSmad2/3 and p300 expression were found significantly increased in all glomerular cell types in both proliferative and nonproliferative GN, while a significant reduction in p57-positive podocytes was observed when compared to controls. Staining for p57 was found to inversely correlate to pSmad2/3 suggesting that glomerular Smad pathway activation is related to down-regulation of p57 expression in proliferative glomerulonephritis. To our knowledge, this is the first study that indicates a relation between the TGF-beta/Smad signalling pathway and the cell cycle regulatory protein p57 in human GN.
  
  
  CONCLUSIONS
  The increased pSmad2/3 staining together with the reduced p57 expression found in biopsy specimens with intense interstitial inflammation, indicate a possible relation between interstitial inflammation, glomerular Smad pathway activation and podocyte cell-cycle deregulation.
authors.affiliation: 1st Department of Pathology, Medical School, University of Athens , Greece .
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Koutroutsos
authors.forename: Theodoros I
authors.initials: TI
authors.lastname: Kassimatis
authors.forename: Alexandros
authors.initials: A
authors.lastname: Nomikos
authors.forename: Ioanna
authors.initials: I
authors.lastname: Giannopoulou
authors.forename: Irene
authors.initials: I
authors.lastname: Theohari
authors.forename: Lydia
authors.initials: L
authors.lastname: Nakopoulou
mesh_terms: D000328:Adult; D002453:Cell Cycle / Q000502:physiology*; D005260:Female; D005921:Glomerulonephritis / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D050199:Podocytes / Q000166:cytology*; D015398:Signal Transduction; D051785:Smad Proteins / Q000096:biosynthesis / Q000502:physiology*; D016212:Transforming Growth Factor beta
chemical_list: D051785:Smad Proteins; D016212:Transforming Growth Factor beta
keywords: Glomerulonephritis; Smad; immunohistochemistry; p57; podocytes