Epithelial to mesenchymal transition in drug-induced gingival overgrowth

Date
2008
DOI
Authors
Lee, Alan Seng Hoo
Version
OA Version
Citation
Abstract
Epithelial to mesenchymal transition (EMT) is involved in embryogenesis, normal wound healing and progression of many tumors of epithelial origin. EMT is associated with loss of proteins associated with the polarized epithelial phenotype, and subsequent transformation into mesenchymal cells, expressing fibroblastic behaviors. Hence, EMT has been shown to play a role in the pathogenesis of organ fibrosis in adult tissues. However, the role of EMT has not been proven in the pathogenesis of drug-induced gingival overgrowth. Transforming growth factor-[beta]1 (TGF-[beta]1) has been shown to best correlate with the extent of fibrosis and has been shown to be involved in the degradation and production of the extracellular matrix, both directly and indirectly, driving the process of EMT. In this study, we investigate if TGF-[beta]1 will contribute to EMT in the context of drug-induced gingival overgrowth. Hence, we use primary gingival epithelial cell cultures obtained from 3 healthy donors and treat them with and without TGF-[beta]1 for 5 days. Western blots, real-time PCR, immunofluorescence and cell morphology studies were carried out to investigate loss of epithelial markers (E-cadherin and ZO-1) and gain in mesenchymal markers (fibronectin, vimentin and a-smooth muscle actin). Our results showed that the gingival epithelial cells, when treated with TGF-[beta]1, had a consistent increase expression of mesenchymal marker, especially fibronectin and a parallel decrease in E-cadherin expression, whereas data from Z0-1, vimentin and a-SMA were not as consistent and conclusive. The TGF-[beta]1-treated cells, when viewed under light microscope, exhibited a spindle-shape appearance without cell-to-cell contacts, in contrast to the control samples which showed a cobble-stone appearance with uniformity in cell shape and size. Our conclusion, despite of the limitations in our experimental design, supports the hypothesis that EMT contributes to the pathogenesis of drug-induced gingival overgrowth.
Description
Thesis (MSD)--Boston University, Henry M. Goldman School of Dental Medicine, 2008 (Dept. of Periodotnology and Oral Biology).
Includes bibliographical references: leaves 48-57.
License
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