{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:34:51Z","timestamp":1787020491426,"version":"build-2736575974"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,6,29]],"date-time":"2024-06-29T00:00:00Z","timestamp":1719619200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,29]],"date-time":"2024-06-29T00:00:00Z","timestamp":1719619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100017160","name":"Beni Suef University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017160","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Oral Health"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Oral lichen planus carries a risk for malignancy. The pathogenesis of the disease is mediated by various inflammatory mediators. Several mediators could be responsible for the oncogenic behavior in certain cases. Hypoxia-inducible factor-1a (HIF-1), and its possible correlation to Galactin-3 (Gal-3) and matrix metalloproteinase-9 (MMP-9) over expression represents an important indicator for malignant transformation. The investigation of these factors may present evidence-based information on malignant transformation of the disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Subjects and methods<\/jats:title>\n                    <jats:p>The study investigated the expression of HIF-1, Gla-3 and MMP-9 in tissue samples of OLP compared to control subjects of un-inflamed gingival overgrowth. 20 biospecimen were allocated in each group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Immunohistochemical findings of OLP showed immunoreactivity for Galectin 3, HIF1a and MMP-9 by most of the epithelial cells. There was a positive correlation between HIF1\u03b1 and MMP-9,\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.9301 (P-value\u2009&lt;\u20090.00001). A positive correlation was detected between Galectin 3 and MMP-9,\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.7292 (P-value\u2009=\u20090.000264) between Galectin 3 and HIF1\u03b1,\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.5893 (P-value\u2009=\u20090.006252).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings confirm the hypothesis that the adaptive pathways to hypoxia as Gal 3 and MMP-9 expressions and their HIF-1 may play a crucial role in carcinogenesis of OLP.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12903-024-04457-6","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T16:31:54Z","timestamp":1719851514000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A critical influence of HIF-1 on MMP-9 and Galectin-3 in oral lichen planus"],"prefix":"10.1186","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9320-295X","authenticated-orcid":false,"given":"Hala H.","family":"Hazzaa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0655-3354","authenticated-orcid":false,"given":"Marwa A. M.","family":"El Shiekh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4875-7534","authenticated-orcid":false,"given":"Osama","family":"Elkashty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0134-1582","authenticated-orcid":false,"given":"Eman","family":"Magdy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7829-6452","authenticated-orcid":false,"given":"Dalia","family":"Riad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1029-9571","authenticated-orcid":false,"given":"Eman","family":"khalifa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7435-6574","authenticated-orcid":false,"given":"Gasser M.","family":"Elewa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3950-3962","authenticated-orcid":false,"given":"Naglaa M.","family":"Kamal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,29]]},"reference":[{"key":"4457_CR1","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.biomaterials.2016.11.040","volume":"116","author":"B -Singh","year":"2017","unstructured":"Singh B, Jang Y, Maharjan S, Kim HJ, Lee AY, Kim S, Gankhuyag N, Yang MS, Choi YJ, Cho MH, Cho CS. Combination therapy with doxorubicin-loaded galactosylated poly (ethyleneglycol)-lithocholic acid to suppress the tumor growth in an orthotopic mouse model of liver cancer. Biomaterials. 2017;116:130\u201344.","journal-title":"Biomaterials"},{"issue":"2","key":"4457_CR2","first-page":"323","volume":"151","author":"L -Zhang","year":"1997","unstructured":"Zhang L, Michelsen C, Cheng X, Zeng T, Priddy R, Rosin MP. Molecular analysis of oral lichen planus. A premalignant lesion? Am J Pathol. 1997;151(2):323\u20137.","journal-title":"Am J Pathol"},{"issue":"4","key":"4457_CR3","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1111\/j.1834-7819.2002.tb00540.x","volume":"47","author":"PB -Sugerman","year":"2002","unstructured":"Sugerman PB, Sabage NW. Oral lichen planus: causes, diagnosis and management. Aust Dent J. 2002;47(4):290\u20137.","journal-title":"Aust Dent J"},{"key":"4457_CR4","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.1007\/s00784-013-0920-8","volume":"17","author":"CA -de Carvalho Fraga","year":"2013","unstructured":"de Carvalho Fraga CA, Alves LR, Marques-Silva L, de Sousa AA, Jorge AS, de Jesus SF, Vilela DN, Pinheiro UB, Jones KM, de Paula AM, Guimar\u00e3es AL. High HIF-1\u03b1 expression genotypes in oral lichen planus. Clin Oral Invest. 2013;17:2011\u20135.","journal-title":"Clin Oral Invest"},{"issue":"47","key":"4457_CR5","doi-asserted-by":"publisher","first-page":"77793","DOI":"10.18632\/oncotarget.12796","volume":"7","author":"FF -Cai","year":"2016","unstructured":"Cai FF, Xu C, Pan X, Cai L, Lin XY, Chen S, Biskup E. Prognostic value of plasma levels of HIF-1a and PGC-1a in breast cancer. Oncotarget. 2016;7(47):77793.","journal-title":"Oncotarget"},{"issue":"1","key":"4457_CR6","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3390\/cancers5010015","volume":"5","author":"Y -Kitajima","year":"2013","unstructured":"Kitajima Y, Miyazaki K. The critical impact of HIF-1\u03b1 on gastric cancer biology. Cancers. 2013;5(1):15\u201326.","journal-title":"Cancers"},{"issue":"3","key":"4457_CR7","doi-asserted-by":"publisher","first-page":"587","DOI":"10.3349\/ymj.2012.53.3.587","volume":"53","author":"C -Ma","year":"2012","unstructured":"Ma C, Wei J, Zhan F, Wang R, Fu K, Wan X, Li Z. Urinary hypoxia-inducible factor-1alpha levels are associated with histologic chronicity changes and renal function in patients with lupus nephritis. Yonsei Med J. 2012;53(3):587\u201392.","journal-title":"Yonsei Med J"},{"issue":"4","key":"4457_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/ar756","volume":"5","author":"A -Giatromanolaki","year":"2003","unstructured":"Giatromanolaki A, Sivridis E, Maltezos E, Athanassou N, Papazoglou D, Gatter KC, Harris AL, Koukourakis MI. Upregulated hypoxia inducible factor-1\u03b1 and-2\u03b1 pathway in rheumatoid arthritis and osteoarthritis. Arthritis Res Ther. 2003;5(4):1\u20139.","journal-title":"Arthritis Res Ther"},{"issue":"2","key":"4457_CR9","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1111\/jcmm.14376","volume":"24","author":"Q -Yang","year":"2020","unstructured":"Yang Q, Sun H, Wang X, Yu X, Zhang J, Guo B, Hexige S. Metabolic changes during malignant transformation in primary cells of oral lichen planus: succinate accumulation and tumour suppression. J Cell Mol Med. 2020;24(2):1179\u201388.","journal-title":"J Cell Mol Med"},{"key":"4457_CR10","doi-asserted-by":"publisher","first-page":"e17","DOI":"10.1017\/S1462399408000719","volume":"10","author":"RY -Yang","year":"2008","unstructured":"Yang RY, Rabinovich GA, Liu FT. Galectins: structure, function and therapeutic potential. Expert Rev Mol Med. 2008;10:e17.","journal-title":"Expert Rev Mol Med"},{"issue":"2","key":"4457_CR11","first-page":"305","volume":"9","author":"A -Krze\u015blak","year":"2004","unstructured":"Krze\u015blak A, Lipi\u0144ska A. Galectin-3 as a multifunctional protein. Cell Mol Biol Lett. 2004;9(2):305\u201328.","journal-title":"Cell Mol Biol Lett"},{"issue":"4","key":"4457_CR12","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1080\/10520295.2020.1800819","volume":"96","author":"V -Pereira-Prado","year":"2021","unstructured":"Pereira-Prado V, Vigil-Bastitta G, S\u00e1nchez-Romero C, Arocena M, Molina-Frechero N, Gonz\u00e1lez-Gonz\u00e1lez R, Meleti M, Bologna-Molina R. Immunoexpression of galectin-3 and its potential relation to hypoxia-inducible factor-1\u03b1 in ameloblastomas. Biotech Histochem. 2021;96(4):296\u2013301.","journal-title":"Biotech Histochem"},{"issue":"2","key":"4457_CR13","first-page":"89","volume":"50","author":"X -Wang","year":"2015","unstructured":"Wang X, Tang G, Sun H. Effect of hypoxia on the proliferation and expressions of hypoxia-inducible factor-1\u03b1, vascular endothelial growth factor and matrix metalloproteinase-9 in keratinocytes obtained from oral lichen planus lesions. Zhonghua Kou Qiang Yi Xue Za Zhi\u2009=\u2009Zhonghua Kouqiang Yixue Zazhi\u2009=\u2009Chinese. J Stomatology. 2015;50(2):89\u201394.","journal-title":"J Stomatology"},{"issue":"9","key":"4457_CR14","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.1248\/bpb.34.1432","volume":"34","author":"MK -Ha","year":"2011","unstructured":"Ha MK, Song YH, Jeong SJ, Lee HJ, Jung JH, Kim B, Song HS, Huh JE, Kim SH. Emodin inhibits proinflammatory responses and inactivates histone deacetylase 1 in hypoxic rheumatoid synoviocytes. Biol Pharm Bull. 2011;34(9):1432\u20137.","journal-title":"Biol Pharm Bull"},{"issue":"2","key":"4457_CR15","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1034\/j.1600-0560.2001.280203.x","volume":"28","author":"XJ -Zhou","year":"2001","unstructured":"Zhou XJ, Sugerman PB, Savage NW, Walsh LJ. Matrix metalloproteinases and their inhibitors in oral lichen planus. J Cutan Pathol. 2001;28(2):72\u201382.","journal-title":"J Cutan Pathol"},{"issue":"4","key":"4457_CR16","doi-asserted-by":"publisher","first-page":"568","DOI":"10.3109\/17435390.2010.537791","volume":"5","author":"R -Wan","year":"2011","unstructured":"Wan R, Mo Y, Chien S, Li Y, Li Y, Tollerud DJ, Zhang Q. The role of hypoxia inducible factor-1\u03b1 in the increased MMP-2 and MMP-9 production by human monocytes exposed to nickel nanoparticles. Nanotoxicology. 2011;5(4):568\u201382.","journal-title":"Nanotoxicology"},{"issue":"2","key":"4457_CR17","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1016\/j.jss.2013.04.061","volume":"184","author":"TA -Mace","year":"2013","unstructured":"Mace TA, Collins AL, Wojcik SE, Croce CM, Lesinski GB, Bloomston M. Hypoxia induces the overexpression of microRNA-21 in pancreatic cancer cells. J Surg Res. 2013;184(2):855\u201360.","journal-title":"J Surg Res"},{"issue":"24","key":"4457_CR18","doi-asserted-by":"publisher","first-page":"11760","DOI":"10.1158\/0008-5472.CAN-07-3233","volume":"67","author":"P -Nangia-Makker","year":"2007","unstructured":"Nangia-Makker P, Raz T, Tait L, Hogan V, Fridman R, Raz A. Galectin-3 cleavage: a novel surrogate marker for matrix metalloproteinase activity in growing breast cancers. Cancer Res. 2007;67(24):11760\u20138.","journal-title":"Cancer Res"},{"issue":"1","key":"4457_CR19","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1080\/01926230252824761","volume":"30","author":"C -Shackelford","year":"2002","unstructured":"Shackelford C, Long G, Wolf J, Okerberg C, Herbert R. Qualitative and quantitative analysis of nonneoplastic lesions in toxicology studies. Toxicol Pathol. 2002;30(1):93\u20136.","journal-title":"Toxicol Pathol"},{"issue":"1","key":"4457_CR20","first-page":"104","volume":"4","author":"-Venktesh Naikmasur","year":"2020","unstructured":"Venktesh Naikmasur, et al. Immunoexpression of Matrix-Metalloproteinase-9 in patients with asymptomatic and symptomatic oral Lichen Planus \u2013 A Clinicopathological Study. Acta Sci Dent Sci. 2020;4(1):104\u201310.","journal-title":"Acta Sci Dent Sci"},{"issue":"9","key":"4457_CR21","doi-asserted-by":"publisher","first-page":"2340","DOI":"10.3390\/cells10092340","volume":"10","author":"MI -Malkov","year":"2021","unstructured":"Malkov MI, Lee CT, Taylor CT. Regulation of the hypoxia-inducible factor (HIF) by pro-inflammatory cytokines. Cells. 2021;10(9):2340.","journal-title":"Cells"},{"key":"4457_CR22","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1007\/s00005-011-0150-1","volume":"59","author":"GA -Scardina","year":"2011","unstructured":"Scardina GA, Ruggieri A, Maresi E, Messina P. Angiogenesis in oral lichen planus: an in vivo and immunohistological evaluation. Arch Immunol Ther Exp. 2011;59:457\u201362.","journal-title":"Arch Immunol Ther Exp"},{"issue":"8","key":"4457_CR23","first-page":"8369","volume":"10","author":"XX -Wang","year":"2017","unstructured":"Wang XX, Sun HY, Yang QZ, Guo B, Sai Y, Zhang J. Hypoxia-inducible factor-1\u03b1 and glucose transporter 1 in the malignant transformation of oral lichen planus. Int J Clin Exp Pathol. 2017;10(8):8369.","journal-title":"Int J Clin Exp Pathol"},{"issue":"8","key":"4457_CR24","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1177\/1535370215593826","volume":"240","author":"FL -de Oliveira","year":"2015","unstructured":"de Oliveira FL, Gatto M, Bassi N, Luisetto R, Ghirardello A, Punzi L, Doria A. Galectin-3 in autoimmunity and autoimmune diseases. Experimental Biology Med. 2015;240(8):1019\u201328.","journal-title":"Experimental Biology Med"},{"issue":"2","key":"4457_CR25","doi-asserted-by":"publisher","first-page":"379","DOI":"10.3390\/ijms19020379","volume":"19","author":"S -Sciacchitano","year":"2018","unstructured":"Sciacchitano S, Lavra L, Morgante A, Ulivieri A, Magi F, De Francesco GP, Bellotti C, Salehi LB, Ricci A. Galectin-3: one molecule for an alphabet of diseases, from a to Z. Int J Mol Sci. 2018;19(2):379.","journal-title":"Int J Mol Sci"},{"issue":"3","key":"4457_CR26","first-page":"689","volume":"19","author":"A -Andisheh-Tadbir","year":"2018","unstructured":"Andisheh-Tadbir A, Mardani M, Malekzadeh M, Tafti TA, Khademi B. Galectin-3 serum levels could help clinicians screen for salivary gland tumor patients. Asian Pac J Cancer Prevention: APJCP. 2018;19(3):689.","journal-title":"Asian Pac J Cancer Prevention: APJCP"},{"issue":"2","key":"4457_CR27","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1111\/odi.13012","volume":"25","author":"J -Ghapanchi","year":"2019","unstructured":"Ghapanchi J, Andisheh-Tadbir A, Torkaman P, Malekzadeh M, Mardani M. Evaluation of the serum levels of galectin\u20103 in patients with oral lichen planus disease. Oral Dis. 2019;25(2):466\u201370.","journal-title":"Oral Dis"},{"key":"4457_CR28","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s10875-006-9022-6","volume":"26","author":"M -Ram","year":"2006","unstructured":"Ram M, Sherer Y, Shoenfeld Y. Matrix metalloproteinase-9 and autoimmune diseases. J Clin Immunol. 2006;26:299\u2013307.","journal-title":"J Clin Immunol"},{"issue":"1","key":"4457_CR29","first-page":"23","volume":"55","author":"V -Paulusov\u00e1","year":"2012","unstructured":"Paulusov\u00e1 V, Laco J, Dr\u00edzhal I, Slez\u00e1k R. Expression of matrix metalloproteinase 9 in patients with oral lichen planus. acta Med (Hradec Kr\u00e1lov\u00e9). 2012;55(1):23\u20136.","journal-title":"acta Med (Hradec Kr\u00e1lov\u00e9)"}],"container-title":["BMC Oral Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12903-024-04457-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12903-024-04457-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12903-024-04457-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T18:02:03Z","timestamp":1719856923000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcoralhealth.biomedcentral.com\/articles\/10.1186\/s12903-024-04457-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,29]]},"references-count":29,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["4457"],"URL":"https:\/\/doi.org\/10.1186\/s12903-024-04457-6","relation":{},"ISSN":["1472-6831"],"issn-type":[{"value":"1472-6831","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,29]]},"assertion":[{"value":"11 November 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 June 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 June 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was conducted during May 2023. The study protocol and consents were reviewed and approved by the Medical Ethical Committees, Al Ahram- Canadian University. Approval number: IRB00012891#45. This study is carried on tissue samples retrieved from the pathology department. Consent of the participants is not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declared no potential conflicts of interest regarding the authorship, research, and\/or publication of this research article.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"756"}}