Τίτλος:
Effect of Smad pathway activation on podocyte cell cycle regulation: An immunohistochemical evaluation
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Koutroutsos, K.
Kassimatis, T.I.
Nomikos, A.
Giannopoulou, I.
Theohari, I.
Nakopoulou, L.
Εκδότης:
LIBRAPHARM/INFORMA HEALTHCARE
Λέξεις-κλειδιά:
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
DOI:
10.3109/0886022X.2014.937664
