{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:58:20Z","timestamp":1788872300818,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,11,4]],"date-time":"2014-11-04T00:00:00Z","timestamp":1415059200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001868","name":"National Science Council","doi-asserted-by":"crossref","award":["NSC100-2632-B-040-001-MY3"],"award-info":[{"award-number":["NSC100-2632-B-040-001-MY3"]}],"id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2015,10]]},"abstract":"\n Background<\/jats:title>\n \n Oral submucous fibrosis (\n OSF<\/jats:styled-content>\n ) is regarded as a pre\u2010cancerous condition with fibrosis in oral subepithelial connective tissue. Hypoxia\u2010inducible factor (\n HIF<\/jats:styled-content>\n )\u20101\u03b1 regulates a wide variety of profibrogenic genes, which are closely associated with tissue fibrosis. The aim of this study was to compare\n HIF<\/jats:styled-content>\n \u20101\u03b1 expression in normal buccal mucosa tissues and\n OSF<\/jats:styled-content>\n specimens and further explore the potential mechanisms that may lead to the induction of\n HIF<\/jats:styled-content>\n \u20101\u03b1 expression.\n <\/jats:p>\n <\/jats:sec>\n \n Method<\/jats:title>\n \n Twenty\u2010five\n OSF<\/jats:styled-content>\n specimens and six normal buccal mucosa were examined by immunohistochemistry. The expression of\n HIF<\/jats:styled-content>\n \u20101\u03b1 from fibroblasts cultured from\n OSF<\/jats:styled-content>\n and normal buccal mucosa was measured by Western blot. Arecoline, a major areca nut alkaloid, was challenged to normal buccal mucosa fibroblasts (\n BMF<\/jats:styled-content>\n s) to elucidate whether\n HIF<\/jats:styled-content>\n \u20101\u03b1 expression could affect by arecoline. In addition, the effects of arecoline on plasminogen activator inhibitor (\n PAI<\/jats:styled-content>\n )\u20101 expression were evaluated in environmental hypoxia.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n HIF<\/jats:styled-content>\n \u20101\u03b1 expression was significantly higher in\n OSF<\/jats:styled-content>\n specimens and expressed mainly by fibroblasts, epithelial cells, and inflammatory cells. Fibroblasts derived from\n OSF<\/jats:styled-content>\n were found to exhibit higher\n HIF<\/jats:styled-content>\n \u20101\u03b1 protein expression than\n BMF<\/jats:styled-content>\n s (\n P<\/jats:italic>\n \u00a0<\u00a00.05). Arecoline was found to upregulate\n HIF<\/jats:styled-content>\n \u20101\u03b1 protein in a dose\u2010dependent manner (\n P<\/jats:italic>\n \u00a0<\u00a00.05). Hypoxia increased arecoline\u2010induced\n PAI<\/jats:styled-content>\n \u20101 protein expression than normoxic conditions (\n P<\/jats:italic>\n \u00a0<\u00a00.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n These results suggest that\n HIF<\/jats:styled-content>\n \u20101\u03b1 expression is significantly upregulated in\n OSF<\/jats:styled-content>\n tissues from areca quid chewers, implying a potential role as a biomarker for local tissue hypoxia. The activation of\n HIF<\/jats:styled-content>\n \u20101\u03b1 may promote fibrogenesis by an increase of\n PAI<\/jats:styled-content>\n \u20101 expression and a subsequent elevation of extracellular matrix production in oral submucosa leading to fibrosis.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/jop.12284","type":"journal-article","created":{"date-parts":[[2014,11,4]],"date-time":"2014-11-04T00:36:38Z","timestamp":1415061398000},"page":"669-673","source":"Crossref","is-referenced-by-count":31,"title":["Hypoxic regulation of plasminogen activator inhibitor\u20101 expression in human buccal mucosa fibroblasts stimulated with arecoline"],"prefix":"10.1111","volume":"44","author":[{"given":"Chung\u2010Hung","family":"Tsai","sequence":"first","affiliation":[{"name":"Institute of Medicine Chung Shan Medical University Taichung Taiwan"},{"name":"Department of Oral Pathology Chung Shan Medical University Hospital Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiuan\u2010Shinn","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Public Health Chung Shan Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Chao","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Dentistry Chung Shan Medical University Hospital Taichung Taiwan"},{"name":"School of Dentistry Chung Shan Medical University Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,11,4]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2005.08.005"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/13556210120091482"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.1998.tb02096.x"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1368-8375(01)00083-5"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0714.2003.00004.x"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1368-8375(01)00045-8"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1368-8375(02)00123-9"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.2006.01272.x"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.2004.01041.x"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2004.00288.x"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2005.05.006"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2006.06.007"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2006.08.009"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2007.00633.x"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.2009.01523.x"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055122"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.23130"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12219"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1366"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2003.12564.x"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90209.2008"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2007.00625.x"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.12.4177"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2005.00435.x"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfma.2012.08.018"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00419.x"}],"container-title":["Journal 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