The Role Of Mesenchymal-epithelial Interaction In The Pathogenesis Of Drug-induced Gingival Overgrowth: A Preliminary Study

OBJECTIVES:The mechanism of nifedipine-induced gingival overgrowth is still unclear. Keratinocyte growth factor and its receptor are involved in hyperplastic lesions of various tissues. The aim of this study is to explore the potential intercellular communication in the development and progression of nifedipine-induced gingival overgrowth.METHODS:Human gingival fibroblasts (HGFs) and keratinocytes (HGKs) were monocultured and cocultured. MTT were used to investigate the effects of NIF on the proliferation of HGFs and HGKs. With different concentrations ( 0, 0.2, 20μg / mL) of nifedipine treatment on the monoculture and coculture systems, the expression of keratinocyte growth factor (KGF) and keratinocyte growth factor receptor (KGFR) mRNA were examined by semi-quantitative reverse transcriptase PCR (RT-PCR) ,while the secretion of KGF and the expression of KGFR on the membrane were analyzed by ELISA and flow cytometry respectively. KGF and KGFR expression changing trends were compared between the monoculture and coculture systems.RESULTS:Nifedipine (0, 0.2, 20μg / mL) had no influence on the cell proliferation for 3 days. The alterations of KGF and KGFR expression in monocultures were not consistent with those in cocultures. The expression of KGF and KGFR genes were significantly upregulated limited to the cocultures .Under the coculture condition, the secretion of KGF was significantly increased by nifedipine in a dose-dependent manner, while it was only significantly upregulated by 20μg / mL nifedipine in monocultures. Moreover, the level of KGFR protein was significantly increased by 0.2μg/mL nifedipine in cocultures, while it was significantly increased by both concentrations of nifedipine in monocultures.CONCLUSIONS:Expression of KGF and KGFR are directly influenced by nifedipine and also indirectly regulated through KGF-KGFR pathway by nifedipine. The interactions between mesenchymal and epithelial cells may play an important role in the molecular mechanism of nifedipine-induced gingival hyperplasia. The in vitro coculture model which is close to the in vivo condition can be of great benefit to further study the mechanism of gingival hyperplasia.