Objectives: Heat shock protein (Hsp)47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagen. Hsp47 is consistently and dramatically upregulated in a variety of fibrotic diseases. However, the involvement of Hsp47 in areca quid-associated oral submucous fibrosis (OSF) is not fully understood. The aim of this study was to compare Hsp47 expression in normal human buccal mucosa and OSF specimens and further to explore the potential mechanisms that may lead to induce Hsp47 expression. Methods: The mRNA levels of Hsp47 from fibroblasts cultured from 20 OSF and 10 normal buccal mucosa fibroblasts (BMFs) were using reverse transcription polymerase chain reaction (RT-PCR). Furthermore, the effect of arecoline, the major areca nut alkaloid, was added to explore the potential mechanism that may lead to induce Hsp47 expression. Furthermore, mitogen-activated protein kinase kinase (MEK) inhibitor U0126, phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and cyclooxygenase-2 (COX-2) inhibitor NS-398 were added to find the possible mechanisms. Results: OSF demonstrated significantly higher Hsp47 mRNA levels expression than BMFs by RT-PCR (p<0.001). In addition, arecoline was also found to elevate Hsp47 expression in a dose-dependent manner (p<0.05). From the RT-PCR analysis, the amount of Hsp47 was about 3.5 fold at a concentration level of 40 ug/ml arecoline compared with control (p<0.05). In addition, pretreatment with pharmacological agents markedly inhibited the arecoline-induced Hsp47 expression (p<0.05). Conclusion: The data presented here demonstrated that Hsp47 expression is significantly upregulated in OSF from areca quid chewers and Hsp47 expression induced by arecoline in fibroblasts may be mediated by MEK, PI3K and COX-2 signal transduction pathway. This study was supported by NSC95-2314-B-040-014

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