{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T04:33:45Z","timestamp":1783226025709,"version":"3.54.6"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T00:00:00Z","timestamp":1633910400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T00:00:00Z","timestamp":1633910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR201911140060"],"award-info":[{"award-number":["ZR201911140060"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Project of Science and Technology Development Plan of Traditional Chinese Medicine in Shandong province","award":["2019-0191"],"award-info":[{"award-number":["2019-0191"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Human Cell"],"published-print":{"date-parts":[[2022,1]]},"DOI":"10.1007\/s13577-021-00625-w","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T16:03:39Z","timestamp":1633968219000},"page":"98-110","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Histone methyltransferase DOT1L mediates the TGF-\u03b21\/Smad3 signaling pathway through epigenetic modification of SYK in myocardial infarction"],"prefix":"10.1007","volume":"35","author":[{"given":"Fei","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiacheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuesong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4811-2816","authenticated-orcid":false,"given":"Yang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,11]]},"reference":[{"key":"625_CR1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2020.617277","volume":"7","author":"Y Wu","year":"2020","unstructured":"Wu Y, Pan N, An Y, Xu M, Tan L, Zhang L. Diagnostic and prognostic biomarkers for myocardial infarction. Front Cardiovasc Med. 2020;7: 617277. https:\/\/doi.org\/10.3389\/fcvm.2020.617277.","journal-title":"Front Cardiovasc Med"},{"issue":"6","key":"625_CR2","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1161\/CIRCRESAHA.115.306565","volume":"118","author":"JG Travers","year":"2016","unstructured":"Travers JG, Kamal FA, Robbins J, Yutzey KE, Blaxall BC. Cardiac fibrosis: the fibroblast awakens. Circ Res. 2016;118(6):1021\u201340. https:\/\/doi.org\/10.1161\/CIRCRESAHA.115.306565.","journal-title":"Circ Res"},{"issue":"6","key":"625_CR3","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1080\/10799893.2020.1772299","volume":"40","author":"D Jin","year":"2020","unstructured":"Jin D, Han F. FOXF1 ameliorates angiotensin II-induced cardiac fibrosis in cardiac fibroblasts through inhibiting the TGF-beta1\/Smad3 signaling pathway. J Recept Signal Transduct Res. 2020;40(6):493\u2013500. https:\/\/doi.org\/10.1080\/10799893.2020.1772299.","journal-title":"J Recept Signal Transduct Res"},{"issue":"5","key":"625_CR4","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1016\/s0092-8674(03)00114-4","volume":"112","author":"J Min","year":"2003","unstructured":"Min J, Feng Q, Li Z, Zhang Y, Xu RM. Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase. Cell. 2003;112(5):711\u201323. https:\/\/doi.org\/10.1016\/s0092-8674(03)00114-4.","journal-title":"Cell"},{"issue":"8","key":"625_CR5","doi-asserted-by":"publisher","first-page":"5588","DOI":"10.1074\/jbc.M111.328138","volume":"287","author":"W Kim","year":"2012","unstructured":"Kim W, Kim R, Park G, Park JW, Kim JE. Deficiency of H3K79 histone methyltransferase Dot1-like protein (DOT1L) inhibits cell proliferation. J Biol Chem. 2012;287(8):5588\u201399. https:\/\/doi.org\/10.1074\/jbc.M111.328138.","journal-title":"J Biol Chem"},{"issue":"3","key":"625_CR6","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1038\/ejhg.2014.110","volume":"23","author":"M Hirokawa","year":"2015","unstructured":"Hirokawa M, Morita H, Tajima T, Takahashi A, Ashikawa K, Miya F, Shigemizu D, Ozaki K, Sakata Y, Nakatani D, Suna S, Imai Y, Tanaka T, Tsunoda T, Matsuda K, Kadowaki T, Nakamura Y, Nagai R, Komuro I, Kubo M. A genome-wide association study identifies PLCL2 and AP3D1-DOT1L-SF3A2 as new susceptibility loci for myocardial infarction in Japanese. Eur J Hum Genet. 2015;23(3):374\u201380. https:\/\/doi.org\/10.1038\/ejhg.2014.110.","journal-title":"Eur J Hum Genet"},{"issue":"1","key":"625_CR7","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1186\/s13148-019-0778-y","volume":"11","author":"L Yang","year":"2019","unstructured":"Yang L, Lei Q, Li L, Yang J, Dong Z, Cui H. Silencing or inhibition of H3K79 methyltransferase DOT1L induces cell cycle arrest by epigenetically modulating c-Myc expression in colorectal cancer. Clin Epigenet. 2019;11(1):199. https:\/\/doi.org\/10.1186\/s13148-019-0778-y.","journal-title":"Clin Epigenet"},{"issue":"6","key":"625_CR8","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1038\/nri2765","volume":"10","author":"A Mocsai","year":"2010","unstructured":"Mocsai A, Ruland J, Tybulewicz VL. The SYK tyrosine kinase: a crucial player in diverse biological functions. Nat Rev Immunol. 2010;10(6):387\u2013402. https:\/\/doi.org\/10.1038\/nri2765.","journal-title":"Nat Rev Immunol"},{"key":"625_CR9","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.biocel.2016.03.001","volume":"74","author":"KH Chen","year":"2016","unstructured":"Chen KH, Hsu HH, Yang HY, Tian YC, Ko YC, Yang CW, Hung CC. Inhibition of spleen tyrosine kinase (syk) suppresses renal fibrosis through anti-inflammatory effects and down regulation of the MAPK-p38 pathway. Int J Biochem Cell Biol. 2016;74:135\u201344. https:\/\/doi.org\/10.1016\/j.biocel.2016.03.001.","journal-title":"Int J Biochem Cell Biol"},{"issue":"3","key":"625_CR10","doi-asserted-by":"publisher","first-page":"505","DOI":"10.3892\/ol.2012.763","volume":"4","author":"C Yan","year":"2012","unstructured":"Yan C, Liu C, Jin Q, Li Z, Tao B, Cai Z. The promoter methylation of the Syk gene in nasopharyngeal carcinoma cell lines. Oncol Lett. 2012;4(3):505\u20138. https:\/\/doi.org\/10.3892\/ol.2012.763.","journal-title":"Oncol Lett"},{"issue":"2","key":"625_CR11","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1007\/s12032-013-0586-8","volume":"30","author":"Z Yang","year":"2013","unstructured":"Yang Z, Huo L, Chen H, Ni B, Xiang J, Kang L, Wang L, Peng J, Yuan Y, Wang J. Hypermethylation and prognostic implication of Syk gene in human colorectal cancer. Med Oncol. 2013;30(2):586. https:\/\/doi.org\/10.1007\/s12032-013-0586-8.","journal-title":"Med Oncol"},{"issue":"1","key":"625_CR12","doi-asserted-by":"publisher","first-page":"89","DOI":"10.4149\/neo_2011_01_89","volume":"58","author":"SW Dong","year":"2011","unstructured":"Dong SW, Ma L, Xu N, Yan HQ, Liu HY, Li YW, Zhang P. Research on the reactivation of Syk expression caused by the inhibition of DNA promoter methylation in the lung cancer. Neoplasma. 2011;58(1):89\u201395. https:\/\/doi.org\/10.4149\/neo_2011_01_89.","journal-title":"Neoplasma"},{"issue":"12","key":"625_CR13","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1161\/CIRCRESAHA.110.223925","volume":"107","author":"E Gao","year":"2010","unstructured":"Gao E, Lei YH, Shang X, Huang ZM, Zuo L, Boucher M, Fan Q, Chuprun JK, Ma XL, Koch WJ. A novel and efficient model of coronary artery ligation and myocardial infarction in the mouse. Circ Res. 2010;107(12):1445\u201353. https:\/\/doi.org\/10.1161\/CIRCRESAHA.110.223925.","journal-title":"Circ Res"},{"issue":"11","key":"625_CR14","doi-asserted-by":"publisher","first-page":"11941","DOI":"10.1096\/fj.201801861R","volume":"33","author":"L Liu","year":"2019","unstructured":"Liu L, Zou J, Guan Y, Zhang Y, Zhang W, Zhou X, Xiong C, Tolbert E, Zhao TC, Bayliss G, Zhuang S. Blocking the histone lysine 79 methyltransferase DOT1L alleviates renal fibrosis through inhibition of renal fibroblast activation and epithelial-mesenchymal transition. FASEB J. 2019;33(11):11941\u201358. https:\/\/doi.org\/10.1096\/fj.201801861R.","journal-title":"FASEB J"},{"key":"625_CR15","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.cbi.2018.07.008","volume":"292","author":"HH Hu","year":"2018","unstructured":"Hu HH, Chen DQ, Wang YN, Feng YL, Cao G, Vaziri ND, Zhao YY. New insights into TGF-beta\/Smad signaling in tissue fibrosis. Chem Biol Interact. 2018;292:76\u201383. https:\/\/doi.org\/10.1016\/j.cbi.2018.07.008.","journal-title":"Chem Biol Interact"},{"key":"625_CR16","doi-asserted-by":"publisher","first-page":"2112","DOI":"10.12659\/MSM.913543","volume":"25","author":"K Liang","year":"2019","unstructured":"Liang K, Ma N, Luo S, Niu W, Wang Y, Bu P. The expression and clinical significance of spleen tyrosine kinase in patients with coronary heart disease. Med Sci Monit. 2019;25:2112\u201321. https:\/\/doi.org\/10.12659\/MSM.913543.","journal-title":"Med Sci Monit"},{"key":"625_CR17","doi-asserted-by":"publisher","first-page":"9346","DOI":"10.12659\/MSM.917287","volume":"25","author":"KH Liu","year":"2019","unstructured":"Liu KH, Zhou N, Zou Y, Yang YY, OuYang SX, Liang YM. Spleen tyrosine kinase (SYK) in the progression of peritoneal fibrosis through activation of the TGF-beta1\/Smad3 signaling pathway. Med Sci Monit. 2019;25:9346\u201356. https:\/\/doi.org\/10.12659\/MSM.917287.","journal-title":"Med Sci Monit"},{"issue":"1","key":"625_CR18","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1080\/0886022X.2020.1764854","volume":"42","author":"L Liu","year":"2020","unstructured":"Liu L, Pang X, Shang W, Feng G, Wang Z, Wang J. miR-136 improves renal fibrosis in diabetic rats by targeting down-regulation of tyrosine kinase SYK and inhibition of TGF-beta1\/Smad3 signaling pathway. Ren Fail. 2020;42(1):513\u201322. https:\/\/doi.org\/10.1080\/0886022X.2020.1764854.","journal-title":"Ren Fail"},{"issue":"4","key":"625_CR19","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1007\/s00412-015-0570-5","volume":"125","author":"H Vlaming","year":"2016","unstructured":"Vlaming H, van Leeuwen F. The upstreams and downstreams of H3K79 methylation by DOT1L. Chromosoma. 2016;125(4):593\u2013605. https:\/\/doi.org\/10.1007\/s00412-015-0570-5.","journal-title":"Chromosoma"},{"key":"625_CR20","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.atherosclerosis.2020.06.002","volume":"308","author":"Y Huang","year":"2020","unstructured":"Huang Y, Urabe G, Zhang M, Li J, Ozer HG, Wang B, Kent KC, Guo LW. Nullifying epigenetic writer DOT1L attenuates neointimal hyperplasia. Atherosclerosis. 2020;308:22\u201331. https:\/\/doi.org\/10.1016\/j.atherosclerosis.2020.06.002.","journal-title":"Atherosclerosis"},{"key":"625_CR21","doi-asserted-by":"publisher","first-page":"4375","DOI":"10.2147\/DDDT.S224909","volume":"13","author":"C Yang","year":"2019","unstructured":"Yang C, Chen Z, Yu H, Liu X. Inhibition of disruptor of telomeric silencing 1-like alleviated renal ischemia and reperfusion injury-induced fibrosis by blocking PI3K\/AKT-mediated oxidative stress. Drug Des Devel Ther. 2019;13:4375\u201387. https:\/\/doi.org\/10.2147\/DDDT.S224909.","journal-title":"Drug Des Devel Ther"},{"key":"625_CR22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2012854118","author":"A Eguchi","year":"2021","unstructured":"Eguchi A, Coleman R, Gresham K, Gao E, Ibetti J, Chuprun JK, Koch WJ. GRK5 is a regulator of fibroblast activation and cardiac fibrosis. Proc Natl Acad Sci USA. 2021. https:\/\/doi.org\/10.1073\/pnas.2012854118.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"6","key":"625_CR23","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1038\/nrneph.2016.48","volume":"12","author":"XM Meng","year":"2016","unstructured":"Meng XM, Nikolic-Paterson DJ, Lan HY. TGF-beta: the master regulator of fibrosis. Nat Rev Nephrol. 2016;12(6):325\u201338. https:\/\/doi.org\/10.1038\/nrneph.2016.48.","journal-title":"Nat Rev Nephrol"},{"issue":"2","key":"625_CR24","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1074\/jbc.RA118.007212","volume":"295","author":"S Maity","year":"2020","unstructured":"Maity S, Muhamed J, Sarikhani M, Kumar S, Ahamed F, Spurthi KM, Ravi V, Jain A, Khan D, Arathi BP, Desingu PA, Sundaresan NR. Sirtuin 6 deficiency transcriptionally up-regulates TGF-beta signaling and induces fibrosis in mice. J Biol Chem. 2020;295(2):415\u201334. https:\/\/doi.org\/10.1074\/jbc.RA118.007212.","journal-title":"J Biol Chem"},{"key":"625_CR25","doi-asserted-by":"publisher","first-page":"3377","DOI":"10.2147\/OTT.S163136","volume":"11","author":"B Ni","year":"2018","unstructured":"Ni B, Li S, Liu Y, Huang Y, Li Z. Prognostic value of spleen tyrosine kinase in human solid tumors. Onco Targets Ther. 2018;11:3377\u201384. https:\/\/doi.org\/10.2147\/OTT.S163136.","journal-title":"Onco Targets Ther"},{"issue":"5","key":"625_CR26","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1007\/s00404-010-1546-6","volume":"283","author":"S Zhao","year":"2011","unstructured":"Zhao S, Sun G, Tony PW, Ma D, Zhao C. Expression and methylation status of the Syk gene in cervical carcinoma. Arch Gynecol Obstet. 2011;283(5):1113\u20139. https:\/\/doi.org\/10.1007\/s00404-010-1546-6.","journal-title":"Arch Gynecol Obstet"},{"key":"625_CR27","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.gde.2016.03.015","volume":"36","author":"X Wang","year":"2016","unstructured":"Wang X, Chen CW, Armstrong SA. The role of DOT1L in the maintenance of leukemia gene expression. Curr Opin Genet Dev. 2016;36:68\u201372. https:\/\/doi.org\/10.1016\/j.gde.2016.03.015.","journal-title":"Curr Opin Genet Dev"},{"issue":"3","key":"625_CR28","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1002\/hep.29881","volume":"68","author":"C Qu","year":"2018","unstructured":"Qu C, Zheng D, Li S, Liu Y, Lidofsky A, Holmes JA, Chen J, He L, Wei L, Liao Y, Yuan H, Jin Q, Lin Z, Hu Q, Jiang Y, Tu M, Chen X, Li W, Lin W, Fuchs BC, Chung RT, Hong J. Tyrosine kinase SYK is a potential therapeutic target for liver fibrosis. Hepatology. 2018;68(3):1125\u201339. https:\/\/doi.org\/10.1002\/hep.29881.","journal-title":"Hepatology"},{"issue":"23","key":"625_CR29","doi-asserted-by":"publisher","first-page":"4512","DOI":"10.1038\/s41388-019-0734-5","volume":"38","author":"A Torres-Hernandez","year":"2019","unstructured":"Torres-Hernandez A, Wang W, Nikiforov Y, Tejada K, Torres L, Kalabin A, Wu Y, Haq MIU, Khan MY, Zhao Z, Su W, Camargo J, Hundeyin M, Diskin B, Adam S, Rossi JAK, Kurz E, Aykut B, Shadaloey SAA, Leinwand J, Miller G. Targeting SYK signaling in myeloid cells protects against liver fibrosis and hepatocarcinogenesis. Oncogene. 2019;38(23):4512\u201326. https:\/\/doi.org\/10.1038\/s41388-019-0734-5.","journal-title":"Oncogene"},{"issue":"2","key":"625_CR30","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1681\/ASN.2019070739","volume":"31","author":"L Zhang","year":"2020","unstructured":"Zhang L, Chen L, Gao C, Chen E, Lightle AR, Foulke L, Zhao B, Higgins PJ, Zhang W. Loss of histone H3 K79 methyltransferase Dot1l facilitates kidney fibrosis by upregulating endothelin 1 through histone deacetylase 2. J Am Soc Nephrol. 2020;31(2):337\u201349. https:\/\/doi.org\/10.1681\/ASN.2019070739.","journal-title":"J Am Soc Nephrol"}],"container-title":["Human Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13577-021-00625-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13577-021-00625-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13577-021-00625-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T18:16:10Z","timestamp":1641406570000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13577-021-00625-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,11]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["625"],"URL":"https:\/\/doi.org\/10.1007\/s13577-021-00625-w","relation":{},"ISSN":["1749-0774"],"issn-type":[{"value":"1749-0774","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,11]]},"assertion":[{"value":"23 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 October 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interests"}},{"value":"All studies were authorized by the Institutional Animal Care and Use Committee of Yantai Mountain Hospital. Experiments were conducted as per the NIH Guidelines on the Use of Laboratory Animals.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}