{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:16:29Z","timestamp":1791994589799,"version":"4.4.0"},"reference-count":57,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,3]],"date-time":"2021-01-03T00:00:00Z","timestamp":1609632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP20K09210"],"award-info":[{"award-number":["JP20K09210"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP20K09210"],"award-info":[{"award-number":["JP20K09210"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP19K09766"],"award-info":[{"award-number":["JP19K09766"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Cigarette smoking (CS) is a major contributing factor in the development of a large number of fatal and debilitating disorders, including degenerative diseases and cancers. Smoking and passive smoking also affect the establishment and maintenance of pregnancy. However, to the best of our knowledge, the effects of smoking on the human endometrium remain poorly understood. In this study, we investigated the regulatory mechanism underlying CS-induced hypoxia-inducible factor (HIF)-1\u03b1 activation using primary human endometrial stromal cells and an immortalized cell line (KC02-44D). We found that the CS extract (CSE) increased reactive oxygen species levels and stimulated HIF-1\u03b1 protein stabilization in endometrial stromal cells, and that CS-induced HIF-1\u03b1-dependent gene expression under non-hypoxic conditions in a concentration- and time-dependent manner. Additionally, we revealed the upregulated expression of a hypoxia-induced gene set following the CSE treatment, even under normoxic conditions. These results indicated that HIF-1\u03b1 might play an important role in CS-exposure-induced cellular stress, inflammation, and endometrial remodeling.<\/jats:p>","DOI":"10.3390\/antiox10010048","type":"journal-article","created":{"date-parts":[[2021,1,3]],"date-time":"2021-01-03T19:54:46Z","timestamp":1609703686000},"page":"48","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Cigarette Smoke Extract Activates Hypoxia-Inducible Factors in a Reactive Oxygen Species-Dependent Manner in Stroma Cells from Human Endometrium"],"prefix":"10.3390","volume":"10","author":[{"given":"Naoko","family":"Kida","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kansai Medical University, 2-3-1 shinmachi-cho, Hirakata 573-1191, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3183-4871","authenticated-orcid":false,"given":"Yoshiyuki","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Department of Human Stress Response Science, Institute of Biomedical Science, Kansai Medical University, Hirakata 573-1010, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiko","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kansai Medical University, 2-3-1 shinmachi-cho, Hirakata 573-1191, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichiro","family":"Nishi","sequence":"additional","affiliation":[{"name":"Department of Human Stress Response Science, Institute of Biomedical Science, Kansai Medical University, Hirakata 573-1010, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Tsuzuki-Nakao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kansai Medical University, 2-3-1 shinmachi-cho, Hirakata 573-1191, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4413-0651","authenticated-orcid":false,"given":"Hidemasa","family":"Bono","sequence":"additional","affiliation":[{"name":"Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima City 739-0046, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Maruyama","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160\u20108582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1110-0827","authenticated-orcid":false,"given":"Kiichi","family":"Hirota","sequence":"additional","affiliation":[{"name":"Department of Human Stress Response Science, Institute of Biomedical Science, Kansai Medical University, Hirakata 573-1010, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7932-6999","authenticated-orcid":false,"given":"Hidetaka","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kansai Medical University, 2-3-1 shinmachi-cho, Hirakata 573-1191, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1056\/NEJMra1308383","article-title":"Global effects of smoking, of quitting, and of taxing tobacco","volume":"370","author":"Jha","year":"2014","journal-title":"N. 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