The upregulation of cystatin C in oral submucous fibrosis

Cystatin C is a 13 kDa non-glycosylated basic protein belonging to cystatin family. It is consistently and dramatically upregulated in a variety of fibrotic diseases. The aim of this study was to compare cystatin C expression in normal human buccal mucosa and oral submucous fibrosis (OSF) specimens and further explore the potential mechanism that may lead to induction of cystatin C expression. Twenty-five OSF specimens and six of normal buccal mucosa were examined by immunohistochemistry. The activity of cystatin C from fibroblasts cultured from OSF and normal buccal mucosa were evaluated by using reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. Furthermore, the effect of arecoline, the major areca nut alkaloid, was explored. Cystatin C expression was significantly higher in OSF specimens (p < 0.05) and expressed mainly by fibroblasts, endothelial cells, and inflammatory cells. OSF demonstrated significantly higher cystatin C expression than normal buccal mucosa fibroblasts both in mRNA and protein levels (p < 0.05). In addition, arecoline was also found to elevate cystatin C mRNA and protein expression in a dose-dependent manner (p < 0.05). Taken together, the data demonstrate that cystatin C expression is significantly upregulated in OSF from areca quid chewers and arecoline may be responsible for the enhanced cystatin C expression in vivo.