{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T01:25:44Z","timestamp":1789003544948,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T00:00:00Z","timestamp":1683504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81960199"],"award-info":[{"award-number":["81960199"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Oral submucous fibrosis (OSF) has a high incidence in Asia countries, but its underlying molecular mechanism was not exploited completely. In this research, we investigated the expression of the phosphatidyl inositol 3\u2010kinase (Pi3k)\/protein kinase B (Akt) pathway and vascular endothelial growth factor (VEGF) in oral submucosal fibrosis, explore the correlation between the Pi3k\/Akt pathway and VEGF, and identify the mechanisms involved in OSF. The pathological changes and fibrosis stages of OSF tissues (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200930, 10 each of early, moderate and advanced OSF) were determined using Haematoxylin\u2013eosin staining (HE) and Masson staining, respectively. Collagen type I (Col\u2010I), Pi3k, Akt, VEGF, TGF\u2010\u03b2 and p\u2010Akt expression was detected using immunohistochemistry, qPCR and WB. The correlation between Pi3k, Akt and VEGF was analysed. Col\u2010I expression increased as OSF progressed. However, their expression was downregulated in normal and moderate to advanced OSF tissues. VEGF expression positively correlated with Pi3k and Akt expression. VEGF expression correlated positively and negatively with the Pi3k inhibitor, LY294002 below and above a concentration of 10\u2009\u03bcM, respectively. VEGF expression correlated positively with the Pi3k\/Ak activator, IGF\u20101. Due to the synergistic effect between Pi3k\/Akt pathway and VEGF on OSF lesions and fibrosis process, targeted Pi3k\/Akt pathway regulation can induce VEGF expression and improve ischemia, ultimately treating OSF.\n                  <\/jats:p>","DOI":"10.1111\/cpr.13491","type":"journal-article","created":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T02:39:48Z","timestamp":1683599988000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Expression and correlation of the Pi3k\/Akt pathway and\n                    <scp>VEGF<\/scp>\n                    in oral submucous fibrosis"],"prefix":"10.1111","volume":"56","author":[{"given":"Yanan","family":"Lin","sequence":"first","affiliation":[{"name":"Hainan General Hospital  Haikou Hainan China"},{"name":"The Affiliated Hainan Hospital of Hainan Medical University  Haikou Hainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1796-5306","authenticated-orcid":false,"given":"Yueying","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Centre for Oral Diseases, West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyu","family":"Xian","sequence":"additional","affiliation":[{"name":"Hainan General Hospital  Haikou Hainan China"},{"name":"The Affiliated Hainan Hospital of Hainan Medical University  Haikou Hainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5654-7414","authenticated-orcid":false,"given":"Xiaoxiao","family":"Cai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Clinical Research Centre for Oral Diseases, West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3381-123X","authenticated-orcid":false,"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"Hainan General Hospital  Haikou Hainan China"},{"name":"The Affiliated Hainan Hospital of Hainan Medical University  Haikou Hainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12836"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20122940"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21197231"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016\u2010008\u20108106\u2010x"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04479"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2021.1964895"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/rda.14076"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2011.00051"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010022\u201023304\u20108"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231911294"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201008013"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2015.2"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.2c02877"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596\u2010022\u201000791\u20107"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413\u2010022\u201000212\u20101"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.28489"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456\u2010020\u201009748\u20104"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010021\u201085534\u20106"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21124449"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.5005\/jp\u2010journals\u201010024\u20102244"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.2174\/1574892813666180227103147"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.09170819"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2018.9713"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2019.12.008"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2019.02.076"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2019.01.005"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm\u201021\u20102213"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020\u2010021\u201000352\u2010w"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.04.040"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.01595"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9091970"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.26355\/eurrev_201810_16022"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b15\u201000026"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000023888"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.13206"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202204287"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1177\/03000605211031433"}],"container-title":["Cell 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