{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T13:41:12Z","timestamp":1791726072468,"version":"4.3.4"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2013,12,1]],"date-time":"2013-12-01T00:00:00Z","timestamp":1385856000000},"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":[[2013,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Schistosomiasis is one of the most common causes of pulmonary arterial hypertension worldwide, but the pathogenic mechanism by which the host inflammatory response contributes to vascular remodeling is unknown. We sought to identify signaling pathways that play protective or pathogenic roles in experimental Schistosoma-induced pulmonary vascular disease via whole-lung transcriptome analysis. Wild-type mice were experimentally exposed to Schistosoma mansoni ova by intraperitoneal sensitization followed by tail-vein augmentation, and the phenotype was assessed by right ventricular catheterization and tissue histology, as well as RNA and protein analysis. Whole-lung transcriptome analysis by microarray and RNA sequencing was performed, and RNA sequencing was analyzed according to two bioinformatics methods. Functional testing of the candidate IL-6 pathway was determined using IL-6 knockout mice and the signal transducers and activators of transcription protein\u20133 (STAT3) inhibitor S3I-201. Wild-type mice exposed to S. mansoni demonstrated increased right ventricular systolic pressure and thickness of the pulmonary vascular media. Whole-lung transcriptome analysis determined that the IL-6\u2013STAT3\u2013nuclear factor of activated T cells c2(NFATc2) pathway was up-regulated, as confirmed by PCR and the immunostaining of lung tissue from S. mansoni\u2013exposed mice and patients who died of the disease. Mice lacking IL-6 or treated with S3I-201 developed pulmonary hypertension, associated with significant intima remodeling after exposure to S. mansoni. Whole-lung transcriptome analysis identified the up-regulation of the IL-6\u2013STAT3\u2013NFATc2 pathway, and IL-6 signaling was found to be protective against Schistosoma-induced intimal remodeling.<\/jats:p>","DOI":"10.1165\/rcmb.2012-0532oc","type":"journal-article","created":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T15:45:16Z","timestamp":1372693516000},"page":"951-959","source":"Crossref","is-referenced-by-count":48,"title":["Protective Role of IL-6 in Vascular Remodeling in\n                    <i>Schistosoma<\/i>\n                    Pulmonary Hypertension"],"prefix":"10.1093","volume":"49","author":[{"given":"Brian B.","family":"Graham","sequence":"first","affiliation":[{"name":"Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine, and"},{"name":"Pulmonary Vascular Research Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Chabon","sequence":"additional","affiliation":[{"name":"Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Kumar","sequence":"additional","affiliation":[{"name":"Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Kolosionek","sequence":"additional","affiliation":[{"name":"Pulmonary Vascular Research Institute, and"},{"name":"Department of Medical Biochemistry and Microbiology, Biomedical Center, University of Uppsala, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liya","family":"Gebreab","sequence":"additional","affiliation":[{"name":"Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Debella","sequence":"additional","affiliation":[{"name":"Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Edwards","sequence":"additional","affiliation":[{"name":"Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina","family":"Diener","sequence":"additional","affiliation":[{"name":"Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted","family":"Shade","sequence":"additional","affiliation":[{"name":"Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gao","family":"Bifeng","sequence":"additional","affiliation":[{"name":"Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Bandeira","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Memorial San Jos\u00e9 Hospital, Universidade de Pernambuco, Recife, Brazil; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghazwan","family":"Butrous","sequence":"additional","affiliation":[{"name":"Pulmonary Vascular Research Institute, and"},{"name":"School of Pharmacy, University of Kent, Kent, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Jones","sequence":"additional","affiliation":[{"name":"Division of Biochemistry and Molecular Genetics, Department of Medicine, University of Colorado School of Medicine, University of Colorado Denver, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Geraci","sequence":"additional","affiliation":[{"name":"Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine, and"},{"name":"Pulmonary Vascular Research Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rubin M.","family":"Tuder","sequence":"additional","affiliation":[{"name":"Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine, and"},{"name":"Pulmonary Vascular Research Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,12,1]]},"reference":[{"key":"2026021904241489200_bib1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/nrmicro801","article-title":"Schistosomiasis","volume":"2","author":"Chitsulo","year":"2004","journal-title":"Nat Rev 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