{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:35:49Z","timestamp":1790678149576,"version":"4.1.0"},"reference-count":36,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,11,25]],"date-time":"2020-11-25T00:00:00Z","timestamp":1606262400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2021,2]]},"DOI":"10.1016\/j.ejphar.2020.173754","type":"journal-article","created":{"date-parts":[[2020,11,25]],"date-time":"2020-11-25T01:57:41Z","timestamp":1606269461000},"page":"173754","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":20,"special_numbering":"C","title":["Significance of nuclear LOXL2 inhibition in fibroblasts and myofibroblasts in the fibrotic process of acute respiratory distress syndrome"],"prefix":"10.1016","volume":"892","author":[{"given":"Ayako","family":"Matsuo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryota","family":"Tanida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigehisa","family":"Yanagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironobu","family":"Tsubouchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Miura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Shigekusa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5581-5635","authenticated-orcid":false,"given":"Nobuhiro","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masamitsu","family":"Nakazato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2020.173754_bib1","first-page":"2526","article-title":"Acute respiratory distress syndrome: the Berlin definition","volume":"307","author":"ARDS Definition Task Force","year":"2012","journal-title":"J. Am. Med. Assoc."},{"key":"10.1016\/j.ejphar.2020.173754_bib2","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/s41598-017-00270-0","article-title":"Comparative analysis of lysyl oxidase (like) family members in pulmonary fibrosis","volume":"7","author":"Aumiller","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejphar.2020.173754_bib3","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1038\/nm.2208","article-title":"Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment","volume":"16","author":"Barry-Hamilton","year":"2010","journal-title":"Nat. Med."},{"key":"10.1016\/j.ejphar.2020.173754_bib4","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1001\/jama.2016.0291","article-title":"Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries","volume":"315","author":"Bellani","year":"2016","journal-title":"J. Am. Med. Assoc."},{"key":"10.1016\/j.ejphar.2020.173754_bib5","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0162636","article-title":"Action of SNAIL1 in cardiac myofibroblasts is important for cardiac fibrosis following hypoxic injury","volume":"11","author":"Biswas","year":"2016","journal-title":"PloS One"},{"key":"10.1016\/j.ejphar.2020.173754_bib6","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1183\/09031936.00196412","article-title":"The fibroproliferative response in acute respiratory distress syndrome: mechanisms and clinical significance","volume":"43","author":"Burnham","year":"2014","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.ejphar.2020.173754_bib7","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.stem.2017.07.011","article-title":"Mesenchymal stem cells in fibrotic disease","volume":"21","author":"El Agha","year":"2017","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.ejphar.2020.173754_bib8","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.abb.2013.12.022","article-title":"Human copper-dependent amine oxidases","volume":"546","author":"Finney","year":"2014","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.ejphar.2020.173754_bib9","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1053\/j.gastro.2018.07.006","article-title":"Simtuzumab is ineffective for patients with bridging fibrosis or compensated cirrhosis caused by nonalcoholic steatohepatitis","volume":"155","author":"Harrison","year":"2018","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ejphar.2020.173754_bib10","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.stem.2014.07.012","article-title":"Repair and regeneration of the respiratory system: complexity, plasticity, and mechanisms of lung stem cell function","volume":"15","author":"Hogan","year":"2014","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.ejphar.2020.173754_bib11","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2011-000545","article-title":"Fibroproliferative changes on high-resolution CT in the acute respiratory distress syndrome predict mortality and ventilator dependency: a prospective observational cohort study","volume":"2","author":"Ichikado","year":"2012","journal-title":"BMJ Open"},{"key":"10.1016\/j.ejphar.2020.173754_bib12","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1074\/jbc.M110.155622","article-title":"Lysyl oxidase-like-2 (LOXL2) is a major isoform in chondrocytes and is critically required for differentiation","volume":"286","author":"Iftikhar","year":"2011","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejphar.2020.173754_bib13","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1136\/gutjnl-2016-312473","article-title":"Selective targeting of lysyl oxidase-like 2 (LOXL2) suppresses hepatic fibrosis progression and accelerates its reversal","volume":"66","author":"Ikenaga","year":"2017","journal-title":"Gut"},{"key":"10.1016\/j.ejphar.2020.173754_bib14","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.molcel.2015.04.012","article-title":"LOXL2 oxidizes methylated TAF10 and controls TFIID-dependent genes during neural progenitor differentiation","volume":"58","author":"Iturbide","year":"2015","journal-title":"Mol. Cell."},{"key":"10.1016\/j.ejphar.2020.173754_bib15","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.aao4881","article-title":"Tensile forces drive a reversible fibroblast-to-myofibroblast transition during tissue growth in engineered clefts","volume":"4","author":"Kollmannsberger","year":"2018","journal-title":"Sci. Adv."},{"key":"10.1016\/j.ejphar.2020.173754_bib16","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1378\/chest.107.1.196","article-title":"Pulmonary fibrosis correlates with outcome in adult respiratory distress syndrome. A study in mechanically ventilated patients","volume":"107","author":"Martin","year":"1995","journal-title":"Chest"},{"key":"10.1016\/j.ejphar.2020.173754_bib17","doi-asserted-by":"crossref","first-page":"L379","DOI":"10.1152\/ajplung.00010.2008","article-title":"Animal models of acute lung injury","volume":"295","author":"Matute-Bello","year":"2008","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"10.1016\/j.ejphar.2020.173754_bib18","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.molcel.2013.10.015","article-title":"Regulation of heterochromatin transcription by Snail1\/LOXL2 during epithelial-to-mesenchymal transition","volume":"52","author":"Millanes-Romero","year":"2013","journal-title":"Mol. Cell."},{"key":"10.1016\/j.ejphar.2020.173754_bib19","doi-asserted-by":"crossref","first-page":"30000","DOI":"10.1074\/jbc.C113.502310","article-title":"MCF-7 cells expressing nuclear associated lysyl oxidase-like 2 (LOXL2) exhibit an epithelial-to-mesenchymal transition (EMT) phenotype and are highly invasive in vitro","volume":"288","author":"Moon","year":"2013","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejphar.2020.173754_bib20","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1002\/hep.30237","article-title":"Simtuzumab for primary sclerosing cholangitis: phase 2 study results with insights on the natural history of the disease","volume":"69","author":"Muir","year":"2019","journal-title":"Hepatology"},{"key":"10.1016\/j.ejphar.2020.173754_bib21","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1136\/thorax.57.7.623","article-title":"Raised plasma concentrations of alpha-defensins in patients with idiopathic pulmonary fibrosis","volume":"57","author":"Mukae","year":"2002","journal-title":"Thorax"},{"key":"10.1016\/j.ejphar.2020.173754_bib22","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/s41467-017-02431-1","article-title":"The lncRNA GATA6-AS epigenetically regulates endothelial gene expression via interaction with LOXL2","volume":"9","author":"Neumann","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ejphar.2020.173754_bib23","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1172\/JCI71386","article-title":"Fibrotic extracellular matrix activates a profibrotic positive feedback loop","volume":"124","author":"Parker","year":"2014","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.ejphar.2020.173754_bib24","doi-asserted-by":"crossref","first-page":"3446","DOI":"10.1038\/sj.emboj.7600781","article-title":"A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and tumor progression","volume":"24","author":"Peinado","year":"2005","journal-title":"EMBO J."},{"key":"10.1016\/j.ejphar.2020.173754_bib25","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/nature14984","article-title":"Hedgehog actively maintains adult lung quiescence and regulates repair and regeneration","volume":"526","author":"Peng","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.ejphar.2020.173754_bib26","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1172\/JCI114369","article-title":"Coordinate regulation of transforming growth factor beta gene expression and cell proliferation in hamster lungs undergoing bleomycin-induced pulmonary fibrosis","volume":"84","author":"Raghow","year":"1989","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.ejphar.2020.173754_bib27","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/S2213-2600(16)30421-0","article-title":"Efficacy of simtuzumab versus placebo in patients with idiopathic pulmonary fibrosis: a randomised, double-blind, controlled, phase 2 trial","volume":"5","author":"Raghu","year":"2017","journal-title":"Lancet Respir. Med."},{"key":"10.1016\/j.ejphar.2020.173754_bib28","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1056\/NEJMra1300575","article-title":"Fibrosis-a common pathway to organ injury and failure","volume":"372","author":"Rockey","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ejphar.2020.173754_bib29","doi-asserted-by":"crossref","first-page":"4403","DOI":"10.1021\/acs.jmedchem.7b00345","article-title":"Identification of 4-(Aminomethyl)-6-(trifluoromethyl)-2-(phenoxy)pyridine derivatives as potent, selective, and orally efficacious inhibitors of the copper-dependent amine oxidase, lysyl oxidase-like 2 (LOXL2)","volume":"60","author":"Rowbottom","year":"2017","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejphar.2020.173754_bib30","first-page":"599","article-title":"Simple, accurate equations for human blood O2 dissociation computations","volume":"46","author":"Severinghaus","year":"1979","journal-title":"J. Appl. Physiol. Respir. Environ. Exerc. Physiol."},{"key":"10.1016\/j.ejphar.2020.173754_bib31","doi-asserted-by":"crossref","DOI":"10.1242\/jcs.203760","article-title":"Reconsidering an active role for G-actin in cytoskeletal regulation","volume":"131","author":"Skruber","year":"2018","journal-title":"J. Cell Sci."},{"key":"10.1016\/j.ejphar.2020.173754_bib32","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1056\/NEJMra1608077","article-title":"Acute respiratory distress syndrome","volume":"377","author":"Thompson","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ejphar.2020.173754_bib33","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nrm809","article-title":"Myofibroblasts and mechano-regulation of connective tissue remodelling","volume":"3","author":"Tomasek","year":"2002","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.ejphar.2020.173754_bib34","first-page":"3530","article-title":"LOXL2, a copper-dependent monoamine oxidase, activates lung fibroblasts through the TGF-beta\/Smad pathway","volume":"42","author":"Wen","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"10.1016\/j.ejphar.2020.173754_bib35","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1042\/bse0520113","article-title":"Lysine post-translational modifications of collagen","volume":"52","author":"Yamauchi","year":"2012","journal-title":"Essays Biochem."},{"key":"10.1016\/j.ejphar.2020.173754_bib36","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1016\/j.cell.2017.07.034","article-title":"Distinct mesenchymal lineages and niches promote epithelial self-renewal and myofibrogenesis in the lung","volume":"170","author":"Zepp","year":"2017","journal-title":"Cell"}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299920308463?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299920308463?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T22:47:25Z","timestamp":1757976445000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299920308463"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2]]},"references-count":36,"alternative-id":["S0014299920308463"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2020.173754","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2021,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Significance of nuclear LOXL2 inhibition in fibroblasts and myofibroblasts in the fibrotic process of acute respiratory distress syndrome","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2020.173754","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"173754"}}