{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:33:45Z","timestamp":1785332025018,"version":"3.55.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to elucidate the potential targets and molecular mechanisms underlying arecoline-induced oral submucous fibrosis through integrated transcriptomic profiling and experimental validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Transcriptomic sequencing was first employed to identify key pathways and targets influenced by arecoline in rat oral mucosa and whole blood. Subsequently,\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments using human primary oral mucosal fibroblasts (hOMFs) were conducted to validate the molecular mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vivo<\/jats:italic>\n                      experiments demonstrated that chronic topical application of arecoline significantly reduced oral opening distance and induced histopathological features of oral submucous fibrosis (OSF), including epithelial atrophy, collagen deposition, and elevated TGF-\u03b2 expression. Transcriptomic analysis revealed significant enrichment of pathways associated with fibrosis, including PPAR signaling, AMPK signaling, p53 signaling, and Hippo signaling pathways.\n                      <jats:italic>In vitro<\/jats:italic>\n                      validation further confirmed that arecoline dose-dependently upregulated \u03b1-SMA and Col1a1 expression, enhanced fibroblast proliferation, and activated Hippo pathway effectors (YAP\/TAZ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings highlight the Hippo signaling pathway as a critical mediator of arecoline-induced OSF, providing novel insights for therapeutic targeting and mechanistic exploration in OSF management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphys.2026.1768602","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T05:40:52Z","timestamp":1772602852000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Uncovering the mechanism of arecoline\u2019s effect on oral submucous fibrosis: integrating transcriptomics and in vitro and in vivo experiments"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhenkui","family":"Liu","sequence":"first","affiliation":[{"name":"School of Chinese Medicine, Hong Kong Baptist University","place":["Hong Kong SAR, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Yi","sequence":"additional","affiliation":[{"name":"The First Hospital of Hunan University of Chinese Medicine, Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanzuo","family":"Zeng","sequence":"additional","affiliation":[{"name":"The First Hospital of Hunan University of Chinese Medicine, Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowei","family":"Chen","sequence":"additional","affiliation":[{"name":"The First Hospital of Hunan University of Chinese Medicine, Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanling","family":"Ning","sequence":"additional","affiliation":[{"name":"The First Hospital of Hunan University of Chinese Medicine, Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiongwei","family":"Tang","sequence":"additional","affiliation":[{"name":"The First Hospital of Hunan University of Chinese Medicine, Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"OuYang","sequence":"additional","affiliation":[{"name":"Institute of Traditional Chinese Medicine Resources, Hunan Academy of Traditional Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s007840050074","article-title":"Cytopathologic effects of arecoline on human gingival fibroblasts in vitro","volume":"3","author":"Chang","year":"1999","journal-title":"Clin. 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