Romanian Society of Pharmaceutical Sciences

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EVIDENCE FOR THE EPITHELIALMESENCHYMAL TRANSITION AS A PATHOGENIC MECHANISM OF PHENYTOININDUCED GINGIVAL OVERGROWTH

CĂTĂLINA PISOSCHI1, CAMELIA STĂNCIULESCU1, CRISTINA MUNTEANU2, ANA MARINA FUSARU3, MONICA BANIŢĂ3

University of Medicine and Pharmacy, 2 Petru Rareş Street, 200349, Craiova, Romania
1Department of Biochemistry,
2Department of Oro-Maxillo-Facial Surgery,
3Department of Histology,

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Gingival overgrowth was reported as a side effect of more than twenty therapeutic agents. Despite the different pharmacological effect of each of these drugs, all seem to act on the gingiva as a secondary target having in common the enlargement of the gingival tissue due to an extracellular matrix accumulation. Previous studies indicated the imbalance of collagen synthesis and breakdown as the main biochemical change, but the precise pathogenic mechanisms are incompletely understood. We investigated the hypothesis that Transforming Growth Factor β1 (TGF-β1) mediated epithelialmesenchymal transition could be involved in the development of phenytoin-induced gingival overgrowth. Immunohistochemistry disclosed an elevated response for TGF-β1 in gingival mucosa associated with a decreased expression of the epithelial marker E-cadherin and an increased number of cells expressing the fibroblast specific protein-1, also known as S100A4, and the transcriptional factors Smad and Snail. Taken together, these data suggest that TGF-β1/Smad/Snail signaling pathway plays an important role in the epithelialmesenchymal transition in phenytoin-induced gingival overgrowth.