Epithelial to mesenchymal transition in gingival overgrowth
Date
2009
DOI
Authors
Zalloum, Charbel
Version
OA Version
Citation
Abstract
Drug therapy and hereditary factors are two of the main causes of gingival overgrowth (GO); both of these forms are associated with increased extracellular matrix production by fibroblasts. Although drug induced gingival overgrowth (DIGO) has been extensively studied, the pathogenesis of this disorder has not been fully understood to date. Epithelial-mesenchymal transition (EMT) is a complex process by which polarized epithelial cells are converted into motile, myofibroblast-like cells. It contributes to pathologies including cancer and fibrosis. TGF-β1 is the main growth factor reported to mediate the initiation and maintenance of the EMT process. The histopathology and expression pattern of connective tissue growth factors in gingival overgrowth has led us to investigate the hypothesis that EMT could contribute to gingival overgrowth and fibrosis. In this study, we are investigating the effect of TGF-β1, HGF and BMP-6 on cultured human gingival epithelial cells regarding EMT and gingival fibrosis. Epithelial cultures from normal gingiva cells were included in this study. To determine the effects of TGF- β l, HGF and BMP-6 stimulation in these cells, the expression of the specific epithelial (E-cadherin) and fibroblastic (Fibronectin) markers were examined by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis. Our results demonstrate that TGF-β1 promotes a dose- and time-dependent decrease in the expression of E-cadherin and increase in the expression of fibronectin. BMP-6 alone or combined with TGF-β1 increased the expression of E-cadherin and decreased the expression of fibronectin, whereas HGF’s effects were not significant. These findings demonstrate that TGF-β1 induces gingival epithelial mesenchymal transdifferentiation, whereas BMP-6 can block this process. More importantly, this study suggests that BMP-6 may be clinically effective in attenuating excessive accumulation of extracellular matrix produced by myofibroblasts in gingival overgrowth.
Description
PLEASE NOTE: This work is protected by copyright. Downloading is restricted to the BU community: please click Download and log in with a valid BU account to access. If you are the author of this work and would like to make it publicly available, please contact open-help@bu.edu.
Thesis (MSD) --Boston University, Henry M. Goldman School of Dental Medicine, 2009 (Department of Periodontology and Oral Biology).
Includes bibliograpic references: leaves 70-84.
Thesis (MSD) --Boston University, Henry M. Goldman School of Dental Medicine, 2009 (Department of Periodontology and Oral Biology).
Includes bibliograpic references: leaves 70-84.
License
This work is protected by copyright. Downloading is restricted to the BU community. If you are the author of this work and would like to make it publicly available, please contact open-help@bu.edu.