@article{3127111,
    title = "Effect of Smad pathway activation on podocyte cell cycle regulation: An immunohistochemical evaluation",
    author = "Koutroutsos, K. and Kassimatis, T.I. and Nomikos, A. and Giannopoulou, I. and Theohari, I. and Nakopoulou, L.",
    journal = "Renal Failure",
    year = "2014",
    volume = "36",
    number = "8",
    pages = "1310-1316",
    publisher = "LIBRAPHARM/INFORMA HEALTHCARE",
    issn = "0886-022X, 1525-6049",
    doi = "10.3109/0886022X.2014.937664",
    keywords = "cyclin dependent kinase inhibitor 1C;  Smad2 protein;  Smad3 protein;  transforming growth factor beta;  Smad protein;  transforming growth factor beta, adult;  article;  cell cycle regulation;  cell nucleus;  controlled study;  correlation analysis;  down regulation;  female;  fibrosing alveolitis;  focal glomerulosclerosis;  human;  human tissue;  immune complex nephritis;  immunoglobulin A nephropathy;  immunohistochemistry;  kidney biopsy;  lupus erythematosus nephritis;  major clinical study;  male;  membranous glomerulonephritis;  minimal change glomerulonephritis;  podocyte;  priority journal;  proliferative glomerulonephritis;  protein expression;  protein phosphorylation;  proteinuria;  signal transduction;  biosynthesis;  cell cycle;  cytology;  glomerulonephritis;  immunohistochemistry;  metabolism;  middle aged;  pathology;  physiology;  podocyte, Adult;  Cell Cycle;  Female;  Glomerulonephritis;  Humans;  Immunohistochemistry;  Male;  Middle Aged;  Podocytes;  Signal Transduction;  Smad Proteins;  Transforming Growth Factor beta",
    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. Conclusion: 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. © 2014 Informa Healthcare USA, Inc. All rights reserved."
}