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As compared with the control (i.e. HUVECs), the protein expressions of GATAs (3\/4\/6) and endMT markers (Snail\/Zeb1\/N\u2010cadherin\/vimentin\/fibronectin\/\u03b1\u2010SMA\/p\u2010Smad2) were significantly reduced, whereas the endothelial\u2010phenotype markers (CD31\/E\u2010cadherin) were significantly increased in silenced <jats:italic>JAG2<\/jats:italic> gene or in silenced <jats:italic>GATA3<\/jats:italic> gene of HUVECs (all <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). As compared with the control, the protein expressions of intercellular signallings (GATAs [3\/4\/6], Jagged1\/2, notch1\/2 and Snail\/Zeb1\/N\u2010cadherin\/vimentin\/fibronectin\/\u03b1\u2010SMA\/p\u2010Smad2) were significantly upregulated in TGF\u2010\u00df\/monocrotaline\u2010treated HUVECs that were significantly reversed by PTU treatment (all <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). By Day 42, the results of animal study demonstrated that the right\u2010ventricular systolic\u2010blood\u2010pressure (RVSBP), RV weight (RVW) and lung injury\/fibrotic scores were significantly increased in MCT group than sham\u2010control (SC) that were reversed in MCT\u2009+\u2009PTU groups, whereas arterial oxygen saturation (%) and vasorelaxation\/nitric oxide production of PA exhibited an opposite pattern of RVW among the groups (all <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). The protein expressions of hypertrophic (\u00df\u2010MHC)\/pressure\u2010overload (BNP)\/oxidative\u2010stress (NOX\u20101\/NOX\u20102) biomarkers in RV and the protein expressions of intercellular signalling (GATAs3\/4\/6, Jagged1\/2, notch1\/2) and endMT markers (Snail\/Zeb1\/N\u2010cadherin\/vimentin\/fibronectin\/TGF\u2010\u00df\/\u03b1\u2010SMA\/p\u2010Smad2) in lung parenchyma displayed an identical pattern of RVW among the groups (all <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). Jagged\u2010Notch\u2010GATAs signalling, endMT markers and RVSBP that were increased in PAH were suppressed by PTU.<\/jats:p>","DOI":"10.1111\/jcmm.17723","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T06:11:19Z","timestamp":1679379079000},"page":"1110-1130","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Jagged\/Notch proteins promote endothelial\u2010mesenchymal transition\u2010mediated pulmonary arterial hypertension via upregulation of the expression of <scp>GATAs<\/scp>"],"prefix":"10.1111","volume":"27","author":[{"given":"Kun\u2010Chen","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine  Kaohsiung 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