{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:39:48Z","timestamp":1792201188906,"version":"4.4.0"},"reference-count":131,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T00:00:00Z","timestamp":1604016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST104-2314-B-255-010-MY3, MOST106-2314-B-002-033-MY2, MOST106- 2314-B-002-034-MY2, MOST107-2314-B-255-009-MY3, MOST107-2314-B-255- 008-MY2"],"award-info":[{"award-number":["MOST104-2314-B-255-010-MY3, MOST106-2314-B-002-033-MY2, MOST106- 2314-B-002-034-MY2, MOST107-2314-B-255-009-MY3, MOST107-2314-B-255- 008-MY2"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPF1G0101, CMRPF1G0102, CMRPF1F0071, CMRPF1H0061, CMRPF1H0062, CMRPF1H0063, CMRPF3E0022, CMRPF3E0023, NMRPF3E0041, NMRPF3E0042, NMRPF3E0043, NMRPF3H0061, NMRPF3H0071, NMRPF3H0072, CMRPF1K0071"],"award-info":[{"award-number":["CMRPF1G0101, CMRPF1G0102, CMRPF1F0071, CMRPF1H0061, CMRPF1H0062, CMRPF1H0063, CMRPF3E0022, CMRPF3E0023, NMRPF3E0041, NMRPF3E0042, NMRPF3E0043, NMRPF3H0061, NMRPF3H0071, NMRPF3H0072, CMRPF1K0071"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Betel 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-\u03b21, 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.<\/jats:p>","DOI":"10.3390\/ijms21218104","type":"journal-article","created":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T09:29:32Z","timestamp":1604050172000},"page":"8104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Genetic Susceptibility and Protein Expression of Extracellular Matrix Turnover-Related Genes in Oral Submucous Fibrosis"],"prefix":"10.3390","volume":"21","author":[{"given":"Ru-Hsiu","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Dentistry, Chang Gung Memorial Hospital, Taipei 105, Taiwan"},{"name":"College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Dentistry, National Taiwan University Medical College, Taipei 100, Taiwan"},{"name":"Department of Dentistry, National Taiwan University Hospital, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia Yu-Fong","family":"Chang","sequence":"additional","affiliation":[{"name":"School of Dentistry, National Taiwan University Medical College, Taipei 100, Taiwan"},{"name":"Department of Dentistry, National Taiwan University Hospital, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hwa","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Chang Gung Memorial Hospital, Taipei 105, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Chi","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Chang Gung Memorial Hospital, Taipei 105, Taiwan"},{"name":"Biomedical Science Team, Department of Nursing, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2068-5380","authenticated-orcid":false,"given":"Jiiang-Huei","family":"Jeng","sequence":"additional","affiliation":[{"name":"School of Dentistry, National Taiwan University Medical College, Taipei 100, Taiwan"},{"name":"Department of Dentistry, National Taiwan University Hospital, Taipei 100, Taiwan"},{"name":"College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan"},{"name":"Department of Dentistry, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,30]]},"reference":[{"key":"ref_1","unstructured":"IARC (2004). 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