{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:35:06Z","timestamp":1788878106705,"version":"build-2803163510"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2011,11,1]],"date-time":"2011-11-01T00:00:00Z","timestamp":1320105600000},"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":[[2011,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In congenital heart block (CHB), binding of maternal anti-SSA\/Ro Abs to fetal apoptotic cardiocytes impairs their removal by healthy cardiocytes and increases urokinase plasminogen activator (uPA)\/uPA receptor (uPAR)-dependent plasmin activation. Because the uPA\/uPAR system plays a role in TGF-\u03b2 activation, we evaluated whether anti-Ro binding to apoptotic cardiocytes enhances plasmin-mediated activation of TGF-\u03b2, thereby promoting a profibrosing phenotype. Supernatants from cocultures of healthy cardiocytes and apoptotic cardiocytes bound by IgG from a mother whose child had CHB (apoptotic-CHB\u2013IgG [apo-CHB\u2013IgG]) exhibited significantly increased levels of active TGF-\u03b2 compared with supernatants from cocultures of healthy cardiocytes and apoptotic cardiocytes preincubated with IgG from a healthy donor. Treatment of the culture medium with anti\u2013TGF-\u03b2 Ab or TGF-\u03b2 inhibitor (SB431542) abrogated the luciferase response, thereby confirming TGF-\u03b2 dependency. Increased uPA levels and activity were present in supernatants generated from cocultures of healthy cardiocytes and apo-CHB\u2013IgG cardiocytes compared with healthy cardiocytes and apoptotic cardiocytes preincubated with IgG from a healthy donor, respectively. Treatment of apo-CHB\u2013IgG cardiocytes with anti-uPAR or anti-uPA Abs or plasmin inhibitor aprotinin prior to coculturing with healthy cardiocytes attenuated TGF-\u03b2 activation. Supernatants derived from cocultures of healthy cardiocytes and apo-CHB\u2013IgG cardiocytes promoted Smad2 phosphorylation and fibroblast transdifferentiation, as evidenced by increased smooth muscle actin and collagen expression, which decreased when fibroblasts were treated with supernatants from cocultures pretreated with uPAR Abs. These data suggested that binding of anti-Ro Abs to apoptotic cardiocytes triggers TGF-\u03b2 activation, by virtue of increasing uPAR-dependent uPA activity, thus initiating and amplifying a cascade of events that promotes myofibroblast transdifferentiation and scar.<\/jats:p>","DOI":"10.4049\/jimmunol.1101288","type":"journal-article","created":{"date-parts":[[2011,10,18]],"date-time":"2011-10-18T05:50:52Z","timestamp":1318917052000},"page":"5392-5401","source":"Crossref","is-referenced-by-count":27,"title":["Binding of Anti-SSA Antibodies to Apoptotic Fetal Cardiocytes Stimulates Urokinase Plasminogen Activator (uPA)\/uPA Receptor-Dependent Activation of TGF-\u03b2 and Potentiates Fibrosis"],"prefix":"10.1093","volume":"187","author":[{"given":"Paraskevi","family":"Briassouli","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, New York University School of Medicine , New York, NY 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Rifkin","sequence":"additional","affiliation":[{"name":"Division of Cell Biology, Department of Medicine, New York University School of Medicine , New York, NY 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M","family":"Clancy","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, New York University School of Medicine , New York, NY 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill P","family":"Buyon","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, New York University School of Medicine , New York, NY 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,11,15]]},"reference":[{"key":"2025032410460340200_r1","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1056\/NEJM197712012972203","article-title":"Association of maternal systemic lupus erythematosus with congenital complete heart block","volume":"297","author":"Chameides","year":"1977","journal-title":"N. 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