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 .