{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T20:33:18Z","timestamp":1775680398077,"version":"3.50.1"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2011,6,1]],"date-time":"2011-06-01T00:00:00Z","timestamp":1306886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Neonatal respiratory distress syndrome can progress to bronchopulmonary dysplasia (BPD), a serious pulmonary fibrotic disorder. Given the involvement of the extrinsic coagulation cascade in animal models of lung fibrosis, we examined its role in BPD. We observed a higher number of neutrophils expressing tissue factor (TF) in bronchoalveolar lavage fluid (BALF) from infants with BPD than from those with uncomplicated respiratory distress syndrome together with a parallel decrease in TF and connective tissue growth factor (CTGF) in BALF supernatants during the disease course. The involvement of coagulation in the fibrotic process associated with BPD was further evaluated by treating primary human colonic myofibroblasts with BALF supernatants from infants with BPD. These human colonic myofibroblasts demonstrated an enhanced C5a- and thrombin-dependent migration. Moreover, they expressed TF in an endothelin-1\u2013dependent manner, with subsequent activation of the extrinsic coagulation cascade and CTGF production mediated by protease-activator receptor-1 signaling. These data provide a novel mechanism for the development of BPD and indicate that endothelin-1 signaling contributes to fibrosis by upregulating a TF\/thrombin amplification loop responsible for CTGF production, and offer novel and specific therapeutic targets for pulmonary fibrotic disease.<\/jats:p>","DOI":"10.4049\/jimmunol.1003756","type":"journal-article","created":{"date-parts":[[2011,4,30]],"date-time":"2011-04-30T02:42:11Z","timestamp":1304131331000},"page":"6568-6575","source":"Crossref","is-referenced-by-count":43,"title":["Endothelin-1 Signaling Promotes Fibrosis In Vitro in a Bronchopulmonary Dysplasia Model by Activating the Extrinsic Coagulation Cascade"],"prefix":"10.1093","volume":"186","author":[{"given":"Konstantinos","family":"Kambas","sequence":"first","affiliation":[{"name":"First Department of Internal Medicine, Democritus University of Thrace , Alexandroupolis 68100 ,","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akrivi","family":"Chrysanthopoulou","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, Democritus University of Thrace , Alexandroupolis 68100 ,","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis","family":"Kourtzelis","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, Democritus University of Thrace , Alexandroupolis 68100 ,","place":["Greece"]},{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania , Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianna","family":"Skordala","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, General University Hospital of Alexandroupolis , Alexandroupolis 68100 \u00a0","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis","family":"Mitroulis","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, Democritus University of Thrace , Alexandroupolis 68100 ,","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stavros","family":"Rafail","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania , Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stergios","family":"Vradelis","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, Democritus University of Thrace , Alexandroupolis 68100 ,","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis","family":"Sigalas","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, General University Hospital of Alexandroupolis , Alexandroupolis 68100 \u00a0","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"You-Qiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania , Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthaios","family":"Speletas","sequence":"additional","affiliation":[{"name":"Department of Immunology and Histocompatibility, University of Thessaly , Larissa ,","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Kolios","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Democritus University of Thrace , Alexandroupolis 68100 ,","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantinos","family":"Ritis","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, Democritus University of Thrace , Alexandroupolis 68100 ,","place":["Greece"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2011,6,1]]},"reference":[{"key":"2025032411293693600_r1","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/j.1538-7836.2009.03368.x","article-title":"The many faces of tissue factor","volume":"7","author":"Mackman","year":"2009","journal-title":"J. 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