{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T04:02:03Z","timestamp":1788235323162,"version":"build-2803163510"},"reference-count":42,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T00:00:00Z","timestamp":1554076800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T00:00:00Z","timestamp":1554076800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"vor","delay-in-days":366,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["17K10205"],"award-info":[{"award-number":["17K10205"]}]},{"name":"Japanese Society for Investigative Dermatology"},{"name":"Lydia O\u2019Leary Memorial Pias Dermatological Foundation"}],"content-domain":{"domain":["jidonline.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Investigative Dermatology"],"published-print":{"date-parts":[[2019,4]]},"DOI":"10.1016\/j.jid.2018.10.027","type":"journal-article","created":{"date-parts":[[2018,11,4]],"date-time":"2018-11-04T09:35:41Z","timestamp":1541324141000},"page":"890-899","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":35,"title":["The Regulation of Skin Fibrosis in Systemic Sclerosis by Extracellular ATP via P2Y2 Purinergic Receptor"],"prefix":"10.1016","volume":"139","author":[{"given":"Liyanage Manosika Buddhini","family":"Perera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Sekiguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Uchiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihito","family":"Uehara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chisako","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahori","family":"Yamazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Yokoyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiko","family":"Ogino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Torii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Hosoi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sei-ichiro","family":"Motegi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"Suppl. 2","key":"10.1016\/j.jid.2018.10.027_bib1","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1186\/ar2186","article-title":"How does endothelial cell injury start? The role of endothelin in systemic sclerosis","volume":"9","author":"Abraham","year":"2007","journal-title":"Arthritis Res Ther"},{"key":"10.1016\/j.jid.2018.10.027_bib2","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/j.pain.2014.02.014","article-title":"Sensitization of cutaneous neuronal purinergic receptors contributes to endothelin-1-induced mechanical hypersensitivity","volume":"155","author":"Barr","year":"2014","journal-title":"Pain"},{"key":"10.1016\/j.jid.2018.10.027_bib3","doi-asserted-by":"crossref","first-page":"232ra50","DOI":"10.1126\/scitranslmed.3008264","article-title":"FibronectinEDA promotes chronic cutaneous fibrosis through Toll-like receptor signaling","volume":"6","author":"Bhattacharyya","year":"2014","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.jid.2018.10.027_bib4","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.imlet.2017.09.011","article-title":"Endogenous ligands of TLR4 promote unresolving tissue fibrosis: implications for systemic sclerosis and its targeted therapy","volume":"195","author":"Bhattacharyya","year":"2018","journal-title":"Immunol Lett"},{"key":"10.1016\/j.jid.2018.10.027_bib5","doi-asserted-by":"crossref","first-page":"11703","DOI":"10.1038\/ncomms11703","article-title":"Tenascin-C drives persistence of organ fibrosis","volume":"7","author":"Bhattacharyya","year":"2016","journal-title":"Nat Commun"},{"key":"10.1016\/j.jid.2018.10.027_bib6","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.bbagen.2008.12.002","article-title":"Endothelin-1 stimulates interleukin-6 secretion from 3T3-L1 adipocytes","volume":"1790","author":"Chai","year":"2009","journal-title":"Biochim Biophys Acta"},{"key":"10.1016\/j.jid.2018.10.027_bib7","doi-asserted-by":"crossref","first-page":"2632","DOI":"10.1002\/art.21974","article-title":"Adenosine A2A receptors in diffuse dermal fibrosis: pathogenic role in human dermal fibroblasts and in a murine model of scleroderma","volume":"54","author":"Chan","year":"2006","journal-title":"Arthritis Rheum"},{"issue":"10103","key":"10.1016\/j.jid.2018.10.027_bib8","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1016\/S0140-6736(17)30933-9","article-title":"Systemic sclerosis","volume":"390","author":"Denton","year":"2017","journal-title":"Lancet"},{"key":"10.1016\/j.jid.2018.10.027_bib9","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/nrrheum.2013.46","article-title":"Targeted therapies for systemic sclerosis","volume":"9","author":"Denton","year":"2013","journal-title":"Nat Rev Rheumatol"},{"issue":"2","key":"10.1016\/j.jid.2018.10.027_bib10","doi-asserted-by":"crossref","first-page":"G417","DOI":"10.1152\/ajpgi.00294.2003","article-title":"Expression of P2Y nucleotide receptors and ectonucleotidases in quiescent and activated rat hepatic stellate cells","volume":"287","author":"Dranoff","year":"2004","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"10.1016\/j.jid.2018.10.027_bib11","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1016\/j.ajpath.2013.08.024","article-title":"Extracellular generation of adenosine by the ectonucleotidases CD39 and CD73 promotes dermal fibrosis","volume":"183","author":"Fern\u00e1ndez","year":"2013","journal-title":"Am J Pathol"},{"key":"10.1016\/j.jid.2018.10.027_bib12","doi-asserted-by":"crossref","first-page":"44638","DOI":"10.1074\/jbc.M203012200","article-title":"Extracellular ATP is an autocrine\/paracrine regulator of hypoxia-induced adventitial fibroblast growth. Signaling through extracellular signal-regulated kinase-1\/2 and the Egr-1 transcription factor","volume":"277","author":"Gerasimovskaya","year":"2002","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.jid.2018.10.027_bib13","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1038\/sj.ki.5001804","article-title":"The role of purinergic P2X7 receptors in the inflammation and fibrosis\u00a0of unilateral ureteral obstruction in mice","volume":"70","author":"Gon\u00e7alves","year":"2006","journal-title":"Kidney Int"},{"key":"10.1016\/j.jid.2018.10.027_bib14","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1046\/j.1523-1747.2003.12261.x","article-title":"Purinergic receptors are part of a functional signaling system for proliferation and differentiation of human epidermal keratinocytes","volume":"120","author":"Greig","year":"2003","journal-title":"J\u00a0Invest Dermatol"},{"key":"10.1016\/j.jid.2018.10.027_bib15","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/sj.jid.5700526","article-title":"Extracellular ATP has stimulatory effects on the expression and release of IL-6 via purinergic receptors in normal human epidermal keratinocytes","volume":"127","author":"Inoue","year":"2007","journal-title":"J\u00a0Invest Dermatol"},{"key":"10.1016\/j.jid.2018.10.027_bib16","doi-asserted-by":"crossref","first-page":"413","DOI":"10.2131\/jts.39.413","article-title":"Purinergic signaling via P2Y receptors up-mediates IL-6 production by liver macrophages\/Kupffer cells","volume":"39","author":"Ishimaru","year":"2014","journal-title":"J\u00a0Toxicol Sci"},{"key":"10.1016\/j.jid.2018.10.027_bib17","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1002\/ddr.10203","article-title":"Flavonoids\u2014novel lead compounds for the development of P2Y2 receptor antagonists","volume":"59","author":"Kaulich","year":"2003","journal-title":"Drug Dev Res"},{"key":"10.1016\/j.jid.2018.10.027_bib18","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1172\/JCI4304","article-title":"Endogenous IL-1\u03b1 from systemic sclerosis fibroblasts induces IL-6 and PDGF-A","volume":"103","author":"Kawaguchi","year":"1999","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.jid.2018.10.027_bib19","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1136\/ard.53.8.506","article-title":"Increased endothelin-1 production in fibroblasts derived from patients with systemic sclerosis","volume":"53","author":"Kawaguchi","year":"1994","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.jid.2018.10.027_bib20","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1136\/annrheumdis-2011-200955","article-title":"Clinical and pathological significance of interleukin 6 overexpression in systemic sclerosis","volume":"71","author":"Khan","year":"2012","journal-title":"Ann Rheum Dis"},{"issue":"10038","key":"10.1016\/j.jid.2018.10.027_bib21","doi-asserted-by":"crossref","first-page":"2630","DOI":"10.1016\/S0140-6736(16)00232-4","article-title":"Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (faSScinate): a phase 2, randomised, controlled trial","volume":"387","author":"Khanna","year":"2016","journal-title":"Lancet"},{"key":"10.1016\/j.jid.2018.10.027_bib22","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.placenta.2015.04.005","article-title":"Hypoxia is an effective stimulus for vesicular release of ATP from human umbilical vein endothelial cells","volume":"36","author":"Lim To","year":"2015","journal-title":"Placenta"},{"issue":"9","key":"10.1016\/j.jid.2018.10.027_bib23","doi-asserted-by":"crossref","first-page":"C779","DOI":"10.1152\/ajpcell.00381.2013","article-title":"Cellular mechanisms of tissue fibrosis. 6. Purinergic signaling and response in fibroblasts and tissue fibrosis","volume":"306","author":"Lu","year":"2014","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.1016\/j.jid.2018.10.027_bib24","doi-asserted-by":"crossref","first-page":"2580","DOI":"10.1096\/fj.12-204677","article-title":"ATP released from cardiac fibroblasts via connexin hemichannels activates profibrotic P2Y2 receptors","volume":"26","author":"Lu","year":"2012","journal-title":"FASEB J"},{"key":"10.1016\/j.jid.2018.10.027_bib25","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1080\/14397595.2016.1206510","article-title":"Oxidative stress markers in blood\u00a0in\u00a0systemic sclerosis: a meta-analysis","volume":"27","author":"Luo","year":"2017","journal-title":"Mod Rheumatol"},{"key":"10.1016\/j.jid.2018.10.027_bib26","doi-asserted-by":"crossref","first-page":"2653","DOI":"10.1161\/ATVBAHA.111.233619","article-title":"Potentiation of platelet-derived growth factor receptor-\u03b2 signaling mediated by integrin-associated MFG-E8","volume":"31","author":"Motegi","year":"2011","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"10.1016\/j.jid.2018.10.027_bib27","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1161\/ATVBAHA.111.232587","article-title":"Pericyte-derived MFG-E8 regulates pathologic angiogenesis","volume":"31","author":"Motegi","year":"2011","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"10.1016\/j.jid.2018.10.027_bib28","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1111\/1346-8138.12642","article-title":"Elevated plasma homocysteine level is possibly associated with skin sclerosis in a series of Japanese patients with systemic sclerosis","volume":"41","author":"Motegi","year":"2014","journal-title":"J\u00a0Dermatol"},{"key":"10.1016\/j.jid.2018.10.027_bib29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-2249.2012.04623.x","article-title":"CD73 and adenosine generation in the creation of regulatory microenvironments","volume":"171","author":"Regateiro","year":"2013","journal-title":"Clin Exp Immunol"},{"key":"10.1016\/j.jid.2018.10.027_bib30","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1164\/rccm.201003-0359OC","article-title":"Extracellular ATP is a danger signal activating P2X7 receptor in lung inflammation and fibrosis","volume":"182","author":"Riteau","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jid.2018.10.027_bib31","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/S0923-1811(01)00128-1","article-title":"Serum levels of interleukin-6 and interleukin-10 correlate with total skin thickness score in patients with systemic sclerosis","volume":"27","author":"Sato","year":"2001","journal-title":"J\u00a0Dermatol Sci"},{"key":"10.1016\/j.jid.2018.10.027_bib32","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1084\/jem.20101805","article-title":"Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection","volume":"208","author":"S\u00e9ror","year":"2011","journal-title":"J\u00a0Exp Med"},{"key":"10.1016\/j.jid.2018.10.027_bib33","doi-asserted-by":"crossref","first-page":"5855","DOI":"10.4049\/jimmunol.0803705","article-title":"Selective oxidation of DNA topoisomerase 1 induces systemic sclerosis in the mouse","volume":"182","author":"Servettaz","year":"2009","journal-title":"J\u00a0Immunol"},{"key":"10.1016\/j.jid.2018.10.027_bib34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0300-483X(00)00272-9","article-title":"Emerging potentials for an antioxidant therapy as a new approach to the treatment of systemic sclerosis","volume":"155","author":"Simonini","year":"2000","journal-title":"Toxicology"},{"key":"10.1016\/j.jid.2018.10.027_bib35","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1038\/jid.2013.163","article-title":"In\u00a0vivo imaging demonstrates ATP release from murine keratinocytes and its involvement in cutaneous inflammation after tape stripping","volume":"133","author":"Takahashi","year":"2013","journal-title":"J\u00a0Invest Dermatol"},{"key":"10.1016\/j.jid.2018.10.027_bib36","doi-asserted-by":"crossref","first-page":"446","DOI":"10.3389\/fpls.2014.00446","article-title":"Extracellular ATP acts as a damage-associated molecular pattern (DAMP) signal in plants","volume":"5","author":"Tanaka","year":"2014","journal-title":"Front Plant Sci"},{"key":"10.1016\/j.jid.2018.10.027_bib37","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nrrheum.2010.102","article-title":"Cellular and molecular aspects of vascular dysfunction in systemic sclerosis","volume":"6","author":"Trojanowska","year":"2010","journal-title":"Nat Rev Rheumatol"},{"key":"10.1016\/j.jid.2018.10.027_bib38","doi-asserted-by":"crossref","first-page":"9072","DOI":"10.1038\/srep09072","article-title":"Protective effect of botulinum toxin A after cutaneous ischemia-reperfusion injury","volume":"5","author":"Uchiyama","year":"2015","journal-title":"Sci Rep"},{"key":"10.1016\/j.jid.2018.10.027_bib39","doi-asserted-by":"crossref","first-page":"34012","DOI":"10.1038\/srep34012","article-title":"Mechanistic insight into the norepinephrine-induced fibrosis in systemic sclerosis","volume":"6","author":"Uehara","year":"2016","journal-title":"Sci Rep"},{"key":"10.1016\/j.jid.2018.10.027_bib40","first-page":"1566","article-title":"Significance of plasma endothelin-1 levels in patients with systemic sclerosis","volume":"19","author":"Yamane","year":"1992","journal-title":"J\u00a0Rheumatol"},{"key":"10.1016\/j.jid.2018.10.027_bib41","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1002\/art.40533","article-title":"Inhibitory regulation of skin fibrosis in systemic sclerosis by apelin\/APJ signaling","volume":"70","author":"Yokoyama","year":"2018","journal-title":"Arthritis Rheumatol"},{"key":"10.1016\/j.jid.2018.10.027_bib43","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1016\/j.ajpath.2017.05.005","article-title":"Adenosine A2a\u00a0receptor blockade diminishes Wnt\/\u03b2-Catenin signaling in a murine model of bleomycin-induced dermal fibrosis","volume":"187","author":"Zhang","year":"2017","journal-title":"Am J Pathol"}],"container-title":["Journal of Investigative Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022202X1832791X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022202X1832791X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T17:14:04Z","timestamp":1758302044000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022202X1832791X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4]]},"references-count":42,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["S0022202X1832791X"],"URL":"https:\/\/doi.org\/10.1016\/j.jid.2018.10.027","relation":{},"ISSN":["0022-202X"],"issn-type":[{"value":"0022-202X","type":"print"}],"subject":[],"published":{"date-parts":[[2019,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The Regulation of Skin Fibrosis in Systemic Sclerosis by Extracellular ATP via P2Y2 Purinergic Receptor","name":"articletitle","label":"Article Title"},{"value":"Journal of Investigative Dermatology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jid.2018.10.027","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology.","name":"copyright","label":"Copyright"}]}}