title: Regulation of hypoxia-inducible factor-1α in human buccal mucosal fibroblasts stimulated with arecoline.
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.
authors.affiliation: School of Applied Chemistry, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Yung-Chuan
authors.initials: YC
authors.lastname: Ho
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.affiliation: School of Public Health, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Shiuan-Shinn
authors.initials: SS
authors.lastname: Lee
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan. Electronic address: cyc@csmu.edu.tw.
authors.forename: Yu-Chao
authors.initials: YC
authors.lastname: Chang
mesh_terms: D001115:Arecoline / Q000494:pharmacology*; D016022:Case-Control Studies; D018679:Cholinergic Agonists / Q000494:pharmacology*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D009061:Mouth Mucosa / Q000378:metabolism*; D009914:Oral Submucous Fibrosis / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D018679:Cholinergic Agonists; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D001115:Arecoline
keywords: arecoline; hypoxia-inducible factor; oral submucous fibrosis; regulatory mechanisms