{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:39:53Z","timestamp":1792190393914,"version":"4.4.0"},"reference-count":39,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T00:00:00Z","timestamp":1681862400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"The National Natural Science Foundation","doi-asserted-by":"crossref","award":["81873717"],"award-info":[{"award-number":["81873717"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"The National Natural Science Foundation","doi-asserted-by":"crossref","award":["82170973"],"award-info":[{"award-number":["82170973"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Clinical Research Fund of the National Clinical Research Center for Geriatric Disorders of Xiangya Hospital","award":["2021LNJJ08"],"award-info":[{"award-number":["2021LNJJ08"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Cellular senescence is strongly associated with fibrosis and tumorigenesis. However, whether the epithelium of oral submucous fibrosis (OSF) undergoes premature senescence remains unclear. This study investigates the roles of senescent epithelial cells in OSF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The immunohistochemistry and Sudan black B staining were performed to identify epithelium senescence in OSF tissues. Arecoline was used to induce human oral keratinocytes (HOKs) senescence. The cell morphology, senescence-associated \u03b2 galactosidase activity, cell counting Kit 8, immunofluorescence, quantitative real-time PCR, and western blot assay were used to identification of senescent HOKs. The enzyme-linked immunosorbent assay was exerted to evaluate the levels of transforming growth factor \u03b21 (TGF-\u03b21) in the supernatants of HOKs treated with or without arecoline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The senescence-associated markers, p16 and p21, were overexpressed in OSF epithelium. These expressions were correlated with alpha-smooth actin (\u03b1-SMA) positively and proliferating cell nuclear antigen (PCNA) negatively. Moreover, Sudan black staining showed that there was more lipofuscin in OSF epithelium. In vitro, HOKs treated with arecoline showed senescence-associated characteristics including enlarged and flattened morphology, senescence-associated \u03b2 galactosidase staining, cell growth arrest, \u03b3H2A.X foci, upregulation of p53, p21, and TGF-\u03b21 protein levels. Moreover, senescent HOKs secreted more TGF-\u03b21.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Senescent epithelial cells are involved in OSF progression and may become a promising target for OSF treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7717\/peerj.15158","type":"journal-article","created":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T03:25:42Z","timestamp":1681874742000},"page":"e15158","source":"Crossref","is-referenced-by-count":7,"title":["Senescent epithelial cells remodel the microenvironment for the progression of oral submucous fibrosis through secreting TGF-\u03b21"],"prefix":"10.7717","volume":"11","author":[{"given":"Zijia","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhui","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanquan","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Xia","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haofeng","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, Hunan, China"},{"name":"Research Center of Oral and Maxillofacial Tumor, Xiangya Hospital, Central South University, Changsha, China"},{"name":"Institute of Oral Precancerous Lesions, Central South University, Changsha, China"},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, 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