{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T14:40:09Z","timestamp":1785768009828,"version":"3.56.0"},"reference-count":46,"publisher":"Korean Society of Otorhinolaryngology-Head and Neck Surgery","issue":"1","license":[{"start":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T00:00:00Z","timestamp":1703721600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770986"],"award-info":[{"award-number":["81770986"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071017"],"award-info":[{"award-number":["82071017"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271134"],"award-info":[{"award-number":["82271134"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2042021kf0093"],"award-info":[{"award-number":["2042021kf0093"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["e-ceo.org"],"crossmark-restriction":true},"short-container-title":["Clin Exp Otorhinolaryngol"],"published-print":{"date-parts":[[2024,2,29]]},"abstract":"<jats:p>Objectives. Hypoxia-inducible factor 1\u03b1 (HIF1\u03b1) and Tet methylcytosine dioxygenase 2 (TET2) have been reported to mediate nasal polypogenesis through the epithelial-to-mesenchymal transition (EMT). Additionally, HIF1\u03b1 can regulate the expression and function of TET2. However, the precise mechanism of how TET2 regulates the EMT through HIF1\u03b1 mediation in nasal epithelial cells is still poorly understood.Methods. Nasal tissue samples were collected from patients with chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), CRS without nasal polyps (CRSsNP), and controls. The expression of HIF1\u03b1 and TET2 was detected using Western blotting and immunohistochemistry. EMT markers (E-cadherin and vimentin) were also evaluated by immunohistochemistry. Primary human nasal epithelial cells (hNECs) were stimulated with CoCl2 to mimic hypoxia. Vitamin C (VC), a TET2 non-specific activator, and small interfering RNA (siRNA) transfection of TET2 were used to further determine the role of TET2 in hypoxia-induced EMT. Finally, reactive oxygen species (ROS) and Nrf2 were measured to explore the downstream consequences of TET2 in hypoxic hNECs.Results. TET2 levels were lower in the nasal epithelium of CRSwNP patients and were positively correlated with E-cadherin but negatively correlated with vimentin in CRS. However, HIF1\u03b1 exhibited the opposite pattern and was negatively correlated with TET2 expression. CoCl2-simulated hypoxia led to EMT and increased HIF1\u03b1 in hNECs in vitro, with simultaneous downregulation of TET2 expression. Addition of VC activated TET2 expression in hNECs, but inhibited EMT and HIF1\u03b1 expression. Furthermore, siRNA knockdown of TET2 contributed to the EMT in CoCl2-simulated hNECs despite the addition of VC. Finally, TET2 regulated the EMT in hypoxic hNECs through Nrf2 expression and ROS generation.Conclusion. TET2 was negatively correlated with HIF1\u03b1 and EMT &lt;i&gt;in vivo&lt;\/i&gt;. TET2 was downregulated by HIF1\u03b1, resulting in the EMT in CoCl2-hypoxic hNECs via regulation of oxidative stress &lt;i&gt;in vitro&lt;\/i&gt;. Hence, TET2 might provide a new therapeutic approach for CRSwNP<\/jats:p>","DOI":"10.21053\/ceo.2023.01340","type":"journal-article","created":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T06:55:52Z","timestamp":1703746552000},"page":"64-77","update-policy":"https:\/\/doi.org\/10.21053\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Downregulation of TET2 Contributes to Nasal Polypogenesis Through Hypoxia-Inducible Factor 1\u03b1-Mediated Epithelial-to-Mesenchymal Transition"],"prefix":"10.21053","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7751-6345","authenticated-orcid":true,"given":"Kunyu","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7751-6345","authenticated-orcid":true,"given":"Yu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1894","reference":[{"key":"ref1","first-page":"1","volume-title":"European position paper on rhinosinusitis and nasal polyps 2020","author":"Fokkens","year":"2020"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1111\/all.12503"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3758"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.07.026"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1007\/s00005-016-0409-7"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2017.33"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2014.01.001"},{"key":"ref8","first-page":"6","volume-title":"TET proteins and 5-methylcytosine oxidation in hematological cancers","author":"Ko","year":"2015"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3589"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-020-01391-5"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf4405"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201109-1706oc"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.134.5.522"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2016.82"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.4193\/rhin18.281"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.4193\/rhino50e2"},{"key":"ref17","first-page":"7405","volume-title":"High-dose vitamin C suppresses the invasion and metastasis of breast cancer cells via inhibiting epithelial-mesenchymal transition","author":"Zeng","year":"2019"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/2510105"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-018-0080-4"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.120177"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.65174"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.04.024"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1111\/all.15384"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1080\/15592294.2014.1003746"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222413239"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-016-0350-y"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1038\/nature19081"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.8001"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1038\/nature25434"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1038\/nature15252"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102916"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.4168\/aair.2022.14.2.254"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.117101"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-21-3013"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.06.017"},{"key":"ref36","first-page":"1233","volume-title":"TET2 mediated demethylation is involved in the protective effect of triptolide on podocytes","author":"Wan","year":"2021"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.13324"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232012249"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.1177\/1945892420982411"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.1002\/alr.22530"},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.1002\/lary.28884"},{"key":"ref42","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21827"},{"key":"ref43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.941608"},{"key":"ref44","doi-asserted-by":"publisher","DOI":"10.1111\/all.15446"},{"key":"ref45","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-80483-y"},{"key":"ref46","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2019-213916"}],"container-title":["Clinical and Experimental Otorhinolaryngology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/e-ceo.org\/upload\/pdf\/ceo-2023-01340.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-ceo.org\/journal\/view.php?doi=10.21053\/ceo.2023.01340","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-ceo.org\/upload\/pdf\/ceo-2023-01340.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T01:36:13Z","timestamp":1710120973000},"score":1,"resource":{"primary":{"URL":"http:\/\/e-ceo.org\/journal\/view.php?doi=10.21053\/ceo.2023.01340"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,29]]},"references-count":46,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,2]]}},"URL":"https:\/\/doi.org\/10.21053\/ceo.2023.01340","relation":{},"ISSN":["1976-8710","2005-0720"],"issn-type":[{"value":"1976-8710","type":"print"},{"value":"2005-0720","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,29]]},"assertion":[{"value":"2023-09-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-28","order":2,"name":"published","label":"Published online","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-29","order":3,"name":"published","label":"Print publication","group":{"name":"publication_history","label":"Publication History"}}]}}