Cheng R.-H.YI-PING WANGJULIA YU-FONG CHANGPan Y.-H.Chang M.-C.JIIANG-HUEI JENG2021-07-072021-07-0720201661-6596https://www.scopus.com/inward/record.uri?eid=2-s2.0-85095579897&doi=10.3390%2fijms21218104&partnerID=40&md5=3891a8d889b14ec93ab0d3c145186f49https://scholars.lib.ntu.edu.tw/handle/123456789/570197Betel quid (BQ) chewing increased the risk of oral cancer and oral submucous fibrosis (OSMF), an oral premalignant disorder (OPMD) with malignant transformation potential. BQ components such as areca nut (AN), trauma by coarse AN fiber, catechin, copper, alkaloids, stimulated reactive oxygen species (ROS), inflammation and cytotoxicity are suggested to be the contributing factors. They may induce tissue inflammation, proliferation of fibroblasts and collagen deposition, myofibroblast differentiation and contraction, collagen cross-links and inhibit collagen phagocytosis, finally leading to the development of OSMF and oral cancer. These events are mediated by BQ components-induced changes of extracellular matrix (ECM) turnover via regulation of TGF-β1, plasminogen activator inhibitor-1 (PAI-1), cystatin, lysyl oxidase (LOX) and tissue inhibitors of metalloproteinases (TIMPs) and metalloproteinases (MMPs). Genetic susceptibility is also involved in these disease processes. Further understanding the molecular mechanisms of BQ-induced OSMF and oral cancer can be helpful for future disease prevention and treatment. ? 2020 by the authors. Licensee MDPI, Basel, Switzerland.[SDGs]SDG3collagen; collagen 1a1; collagen 1a2; collagenase; collagenase 1; cystatin C; gelatinase A; gelatinase B; metalloproteinase; plasminogen activator inhibitor 1; protein lysine 6 oxidase; stromelysin; tissue inhibitor of metalloproteinase; transforming growth factor beta; unclassified drug; scleroprotein; betel quid; clinical feature; extracellular matrix; gene expression; genetic susceptibility; histopathology; human; mouth disease; protein expression; Review; risk factor; adverse event; Areca; extracellular matrix; genetic predisposition; metabolism; mouth disease; pathology; Areca; Extracellular Matrix; Extracellular Matrix Proteins; Genetic Predisposition to Disease; Humans; Oral Submucous Fibrosisreview10.3390/ijms21218104331431012-s2.0-85095579897