{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T20:59:49Z","timestamp":1793825989856,"version":"4.6.1"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing","doi-asserted-by":"publisher","award":["cstc2018jcyjA0153"],"award-info":[{"award-number":["cstc2018jcyjA0153"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81,970,203"],"award-info":[{"award-number":["81,970,203"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31,800,976"],"award-info":[{"award-number":["31,800,976"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","thelancet.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["EBioMedicine"],"published-print":{"date-parts":[[2021,5]]},"DOI":"10.1016\/j.ebiom.2021.103370","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T00:02:16Z","timestamp":1620345736000},"page":"103370","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":45,"special_numbering":"C","title":["TNAP is a novel regulator of cardiac fibrosis after myocardial infarction by mediating TGF-\u03b2\/Smads and ERK1\/2 signaling pathways"],"prefix":"10.1016","volume":"67","author":[{"given":"Xiaocheng","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyou","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuesong","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanglei","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0507-897X","authenticated-orcid":false,"given":"Dongying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ebiom.2021.103370_bib0001","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1016\/j.jacc.2017.06.032","article-title":"2017 AHA\/ACC clinical performance and quality measures for adults with ST-elevation and non-ST-elevation myocardial infarction: a report of the American college of cardiology\/American heart association task force on performance measures","volume":"70","author":"Jneid","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.ebiom.2021.103370_bib0002","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1161\/CIRCRESAHA.116.303577","article-title":"The biological basis for cardiac repair after myocardial infarction: from inflammation to fibrosis","volume":"119","author":"Prabhu","year":"2016","journal-title":"Circ Res"},{"key":"10.1016\/j.ebiom.2021.103370_bib0003","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1016\/j.jacc.2018.02.021","article-title":"Myocardial interstitial fibrosis in heart failure: biological and translational perspectives","volume":"71","author":"Gonz\u00e1lez","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.ebiom.2021.103370_bib0004","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nrneph.2017.60","article-title":"Alkaline phosphatase: a novel treatment target for cardiovascular disease in CKD","volume":"13","author":"Haarhaus","year":"2017","journal-title":"Nat Rev Nephrol"},{"key":"10.1016\/j.ebiom.2021.103370_bib0005","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1258\/000456306776865179","article-title":"The effect of alkaline phosphatase inhibitors on intracellular lipid accumulation in preadipocytes isolated from human mammary tissue","volume":"43","author":"Ali","year":"2006","journal-title":"Ann Clin Biochem"},{"key":"10.1016\/j.ebiom.2021.103370_bib0006","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1093\/cercor\/bhh021","article-title":"Areal and subcellular localization of the ubiquitous alkaline phosphatase in the primate cerebral cortex: evidence for a role in neurotransmission","volume":"14","author":"Fonta","year":"2004","journal-title":"Cereb Cortex"},{"key":"10.1016\/j.ebiom.2021.103370_bib0007","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1161\/CIRCULATIONAHA.109.851873","article-title":"Relation between alkaline phosphatase, serum phosphate, and all-cause or cardiovascular mortality","volume":"120","author":"Tonelli","year":"2009","journal-title":"Circulation"},{"key":"10.1016\/j.ebiom.2021.103370_bib0008","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1093\/eurheartj\/ehs419","article-title":"Serum alkaline phosphatase is a predictor of mortality, myocardial infarction, or stent thrombosis after implantation of coronary drug-eluting stent","volume":"34","author":"Park","year":"2013","journal-title":"Eur Heart J"},{"key":"10.1016\/j.ebiom.2021.103370_bib0009","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.atherosclerosis.2018.05.012","article-title":"The coronary calcium paradox: yet another step towards the differentiation between stable and rupture-prone coronary plaques?","volume":"274","author":"Korosoglou","year":"2018","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.ebiom.2021.103370_bib0010","doi-asserted-by":"crossref","DOI":"10.1242\/jcs.234948","article-title":"TNAP limits TGF-\u03b2-dependent cardiac and skeletal muscle fibrosis by inactivating the SMAD2\/3 transcription factors","volume":"132","author":"Arn\u00f2","year":"2019","journal-title":"J Cell Sci"},{"key":"10.1016\/j.ebiom.2021.103370_bib0011","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.119.012486","article-title":"Homoarginine supplementation prevents left ventricular dilatation and preserves systolic function in a model of coronary artery disease","volume":"8","author":"Rodionov","year":"2019","journal-title":"J Am Heart Assoc"},{"key":"10.1016\/j.ebiom.2021.103370_bib0012","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41419-020-2243-4","article-title":"TNAP inhibition attenuates cardiac fibrosis induced by myocardial infarction through deactivating TGF-\u03b21\/Smads and activating P53 signaling pathways","volume":"11","author":"Gao","year":"2020","journal-title":"Cell Death Dis"},{"key":"10.1016\/j.ebiom.2021.103370_bib0013","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.neuro.2005.08.003","article-title":"Neurobehavioral effects of tetramisole in mice","volume":"27","author":"Mohammad","year":"2006","journal-title":"Neurotoxicology"},{"key":"10.1016\/j.ebiom.2021.103370_bib0014","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/978-94-017-7197-9_12","article-title":"Tetramisole and levamisole suppress neuronal activity independently from their inhibitory action on tissue non-specific alkaline phosphatase in mouse cortex","volume":"76","author":"Nowak","year":"2015","journal-title":"Subcell Biochem"},{"key":"10.1016\/j.ebiom.2021.103370_bib0015","doi-asserted-by":"crossref","first-page":"g7647","DOI":"10.1136\/bmj.g7647","article-title":"Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation","volume":"350","author":"Shamseer","year":"2015","journal-title":"BMJ"},{"key":"10.1016\/j.ebiom.2021.103370_bib0016","series-title":"The Newcastle\u2013Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses","author":"Wells","year":"2020"},{"key":"10.1016\/j.ebiom.2021.103370_bib0017","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1016\/j.jacc.2015.04.026","article-title":"Circulating biomarkers of myocardial fibrosis: the need for a reappraisal","volume":"65","author":"L\u00f3pez","year":"2015","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.ebiom.2021.103370_bib0018","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/s41569-019-0286-y","article-title":"Heart failure as interstitial cancer: emergence of a malignant fibroblast phenotype. Heart failure as interstitial cancer: emergence of a malignant fibroblast phenotype","volume":"17","author":"Oatmen","year":"2020","journal-title":"Nat Rev Cardiol"},{"key":"10.1016\/j.ebiom.2021.103370_bib0019","doi-asserted-by":"crossref","first-page":"3770","DOI":"10.1172\/JCI94753","article-title":"Fibroblast-specific TGF-beta-Smad2\/3 signaling underlies cardiac fibrosis","volume":"127","author":"Khalil","year":"2017","journal-title":"J Clin Invest"},{"key":"10.1016\/j.ebiom.2021.103370_bib0020","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2019.101151","article-title":"Vascular peroxidase 1 is a novel regulator of cardiac fibrosis after myocardial infarction","volume":"22","author":"Liu","year":"2019","journal-title":"Redox Biol"},{"key":"10.1016\/j.ebiom.2021.103370_bib0021","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1080\/15384101.2018.1480221","article-title":"The ERK\/CREB pathway is involved in the c-Ski expression induced by low TGF-\u03b21 concentrations during primary fibroblast proliferation","volume":"17","author":"Li","year":"2018","journal-title":"Cell Cycle"},{"key":"10.1016\/j.ebiom.2021.103370_bib0022","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1161\/01.CIR.0000136995.83451.1D","article-title":"Role for matrix metalloproteinase-2 in oxidized low-density lipoprotein-induced activation of the sphingomyelin\/ceramide pathway and smooth muscle cell proliferation","volume":"110","author":"Aug\u00e9","year":"2004","journal-title":"Circulation"},{"key":"10.1016\/j.ebiom.2021.103370_bib0023","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1111\/eci.12752","article-title":"Alkaline phosphatase and prognosis in patients with coronary artery disease","volume":"47","author":"Ndrepepa","year":"2017","journal-title":"Eur J Clin Invest"},{"key":"10.1016\/j.ebiom.2021.103370_bib0024","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2018-025648","article-title":"Prognostic impact of alkaline phosphatase for in-hospital mortality in patients with acute coronary syndrome: a prospective cohort study in China","volume":"9","author":"Yu","year":"2019","journal-title":"BMJ Open"},{"key":"10.1016\/j.ebiom.2021.103370_bib0025","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1093\/eurheartj\/ehaa033","article-title":"Impact of myocardial fibrosis on left ventricular remodelling, recovery, and outcome after transcatheter aortic valve implantation in different haemodynamic subtypes of severe aortic stenosis","volume":"41","author":"Puls","year":"2020","journal-title":"Eur Heart J"},{"key":"10.1016\/j.ebiom.2021.103370_bib0026","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1056\/NEJMoa1002659","article-title":"Myocardial fibrosis as an early manifestation of hypertrophic cardiomyopathy","volume":"363","author":"Ho","year":"2010","journal-title":"N Engl J Med"},{"key":"10.1016\/j.ebiom.2021.103370_bib0027","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.bone.2014.06.040","article-title":"Tissue-nonspecific alkaline phosphatase deficiency causes abnormal craniofacial bone development in the Alpl(-\/-) mouse model of infantile hypophosphatasia","volume":"67","author":"Liu","year":"2014","journal-title":"Bone"},{"key":"10.1016\/j.ebiom.2021.103370_bib0028","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/ng0995-45","article-title":"Mice lacking tissue non-specific alkaline phosphatase die from seizures due to defective metabolism of vitamin B-6","volume":"11","author":"Waymire","year":"1995","journal-title":"Nat Genet"},{"key":"10.1016\/j.ebiom.2021.103370_bib0029","doi-asserted-by":"crossref","first-page":"4143","DOI":"10.1093\/hmg\/ddw248","article-title":"Neurodevelopmental alterations and seizures developed by mouse model of infantile hypophosphatasia are associated with purinergic signalling deregulation","volume":"25","author":"Sebastian-Serrano","year":"2016","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.ebiom.2021.103370_bib0030","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.115.002499","article-title":"Transgenic overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in vascular endothelium results in generalized arterial calcification","volume":"4","author":"Savinov","year":"2015","journal-title":"J Am Heart Assoc"},{"key":"10.1016\/j.ebiom.2021.103370_bib0031","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1161\/CIRCRESAHA.114.302653","article-title":"Cardiomyocyte-specific transforming growth factor \u03b2 suppression blocks neutrophil infiltration, augments multiple cytoprotective cascades, and reduces early mortality after myocardial infarction","volume":"114","author":"Rainer","year":"2014","journal-title":"Circ Res"},{"key":"10.1016\/j.ebiom.2021.103370_bib0032","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.neulet.2010.09.013","article-title":"Knockdown of tissue nonspecific alkaline phosphatase impairs neural stem cell proliferation and differentiation","volume":"485","author":"Kermer","year":"2010","journal-title":"Neurosci Lett"},{"key":"10.1016\/j.ebiom.2021.103370_bib0033","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/sj.cr.7290105","article-title":"MAPK signal pathways in the regulation of cell proliferation in mammalian cells","volume":"12","author":"Zhang","year":"2002","journal-title":"Cell Res"},{"key":"10.1016\/j.ebiom.2021.103370_bib0034","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.ejphar.2016.07.053","article-title":"Activin A stimulates the proliferation and differentiation of cardiac fibroblasts via the ERK1\/2 and p38-MAPK pathways","volume":"789","author":"Hu","year":"2016","journal-title":"Eur J Pharmacol"},{"key":"10.1016\/j.ebiom.2021.103370_bib0035","first-page":"171","article-title":"PBI-4050 reduces pulmonary hypertension, lung fibrosis, and right ventricular dysfunction in heart failure","volume":"116","author":"Nguyen","year":"2020","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.ebiom.2021.103370_bib0036","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.jacc.2011.10.887","article-title":"Cardiac-specific deletion of SOCS-3 prevents development of left ventricular remodeling after acute myocardial infarction","volume":"59","author":"Oba","year":"2012","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.ebiom.2021.103370_bib0037","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.lfs.2007.10.003","article-title":"Activity and expression of ecto-5\u2032-nucleotidase\/CD73 are increased during phenotype conversion of a hepatic stellate cell line","volume":"82","author":"Andrade","year":"2008","journal-title":"Life Sci"},{"key":"10.1016\/j.ebiom.2021.103370_bib0038","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0158981","article-title":"Alkaline phosphatase, soluble extracellular adenine nucleotides, and adenosine production after infant cardiopulmonary bypass","volume":"11","author":"Davidson","year":"2016","journal-title":"PLoS ONE"},{"key":"10.1016\/j.ebiom.2021.103370_bib0039","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.freeradbiomed.2020.04.008","article-title":"Reactive oxygen species (ROS) generation as an underlying mechanism of inorganic phosphate (P)-induced mineralization of osteogenic cells","volume":"153","author":"Khalid","year":"2020","journal-title":"Free Radic Biol Med"},{"key":"10.1016\/j.ebiom.2021.103370_bib0040","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.bbrc.2016.01.077","article-title":"High inorganic phosphate causes DNMT1 phosphorylation and subsequent fibrotic fibroblast activation","volume":"472","author":"Tan","year":"2016","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.ebiom.2021.103370_bib0041","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.bone.2018.10.013","article-title":"Tissue nonspecific alkaline phosphatase promotes calvarial progenitor cell cycle progression and cytokinesis via Erk1,2","volume":"120","author":"Nam","year":"2019","journal-title":"Bone"},{"key":"10.1016\/j.ebiom.2021.103370_bib0042","doi-asserted-by":"crossref","first-page":"6071","DOI":"10.1038\/sj.onc.1210706","article-title":"Protein kinase WNK2 inhibits cell proliferation by negatively modulating the activation of MEK1\/ERK1\/2","volume":"26","author":"Moniz","year":"2007","journal-title":"Oncogene"},{"key":"10.1016\/j.ebiom.2021.103370_bib0043","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s00204-014-1249-z","article-title":"Aristolochic acid-induced apoptosis and G2 cell cycle arrest depends on ROS generation and MAP kinases activation","volume":"89","author":"Romanov","year":"2015","journal-title":"Arch Toxicol"},{"key":"10.1016\/j.ebiom.2021.103370_bib0044","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1083\/jcb.200804038","article-title":"Erk1\/2 MAP kinases are required for epidermal G2\/M progression","volume":"185","author":"Dumesic","year":"2009","journal-title":"J Cell Biol"}],"container-title":["EBioMedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352396421001638?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352396421001638?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T19:32:57Z","timestamp":1778873577000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2352396421001638"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5]]},"references-count":44,"alternative-id":["S2352396421001638"],"URL":"https:\/\/doi.org\/10.1016\/j.ebiom.2021.103370","relation":{},"ISSN":["2352-3964"],"issn-type":[{"value":"2352-3964","type":"print"}],"subject":[],"published":{"date-parts":[[2021,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"TNAP is a novel regulator of cardiac fibrosis after myocardial infarction by mediating TGF-\u03b2\/Smads and ERK1\/2 signaling pathways","name":"articletitle","label":"Article Title"},{"value":"EBioMedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ebiom.2021.103370","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Author(s). Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"103370"}}