Raised keratinocyte growth factor-1 expression in oral submucous fibrosis in vivo and upregulated by arecoline in human buccal mucosal fibroblasts in vitro

BACKGROUND: Keratinocyte growth factor-1 (KGF-1) is the seventh member of the fibroblast growth factor family. KGF-1 is produced by mesenchymal cells such as fibroblasts and upregulated in a variety of hyperplastic tissues. Currently, there is limited information about the regulation of KGF-1 expression in areca quid-associated oral submucous fibrosis (OSF). The aim of the study was to compare KGF-1 expression in normal human buccal mucosa and OSF specimens and further to explore the potential mechanism that may lead to induce KGF-1 expression. METHODS: The expression of KGF-1 from fibroblasts cultured from OSF and normal buccal mucosa were using reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. In addition, arecoline, a major areca nut alkaloid, was challenged to normal buccal mucosa fibroblasts (BMFs) to elucidate whether KGF-1 expression could affect by arecoline. Furthermore, 25 OSF specimens and six normal buccal mucosa specimens were examined by immunohistochemistry. RESULTS: Fibroblasts derived from OSF were found to exhibit higher KGF-1 expression than BMFs both in mRNA and protein levels (P < 0.05). In addition, upregulation of KGF-1 mRNA gene and protein expression were found in BMFs stimulated by arecoline (P < 0.05). From the results of immunohistochemistry, KGF-1 expression was significantly higher in OSF specimens and expressed mainly by fibroblasts, endothelial cells, inflammatory cells, and epithelial cells. CONCLUSIONS: Taken together, these results suggest that KGF-1 expression is significantly upregulated in OSF tissues from areca quid chewers and arecoline may be responsible for the enhanced KGF-1 expression in vivo.