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  • Title: Regulation of hypoxia-inducible factor-1α in human buccal mucosal fibroblasts stimulated with arecoline.
    Author: Ho YC, Yang SF, Lee SS, Chang YC.
    Journal: J Formos Med Assoc; 2017 Jun; 116(6):484-487. PubMed ID: 28365254.
    Abstract:
    Hypoxia-inducible factor (HIF)-1α is consistently and dramatically upregulated in a variety of fibrotic diseases. The aim of this study was to compare HIF-1α expression from fibroblasts derived from human normal buccal mucosa and oral submucous fibrosis (OSF) specimens and further to explore the potential mechanisms that may lead to induce HIF-1α expression. OSF buccal mucosal fibroblasts (BMFs) demonstrated significantly higher HIF-1α mRNA expression than normal BMFs (p<0.005). Arecoline, the major areca nut alkaloid, was also found to elevate HIF-1α mRNA expression in a dose-dependent manner (p<0.05). Moreover, arecoline-induced HIF-1α expression was downregulated by mitogen-activated protein kinase inhibitor U0126, phosphatidylinositol 3-kinase inhibitor LY294002, p38 inhibitor SB203580, cyclooxygenase-2 inhibitor NS-398, and glutathione precursor N-acetyl-L-cysteine (p<0.05). Taken together, hypoxia plays an important role in the pathogenesis of areca quid chewing-associated OSF. These pharmacological agents may be further used as chemoprevention agents for OSF.
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