{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:09:01Z","timestamp":1790780941002,"version":"4.1.0"},"reference-count":46,"publisher":"American Society for Clinical Investigation","issue":"9","license":[{"start":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T00:00:00Z","timestamp":1652054400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"American Autoimmune Related Disease Foundation","award":["Young Investigator Award"],"award-info":[{"award-number":["Young Investigator Award"]}]},{"name":"the Edward T. and Ellen K. Dryer Early Career Professorship","award":["Endowment funds"],"award-info":[{"award-number":["Endowment funds"]}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["UM1-AI144298-01,R01AI097134"],"award-info":[{"award-number":["UM1-AI144298-01,R01AI097134"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"crossref","award":["K24AR063120,R01AR070148"],"award-info":[{"award-number":["K24AR063120,R01AR070148"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,9]]},"abstract":"<jats:p>\n                    Binding of the bromodomain and extraterminal domain proteins (BETs) to acetylated histone residues is critical for gene transcription. We sought to determine the antifibrotic efficacy and potential mechanisms of BET inhibition in systemic sclerosis (SSc). Blockade of BETs was done using a pan-BET inhibitor, JQ1; BRD2 inhibitor, BIC1; or BRD4 inhibitors AZD5153 or ARV825. BET inhibition, specifically BRD4 blockade, showed antifibrotic effects in an animal model of SSc and in patient-derived diffuse cutaneous SSc (dcSSc) fibroblasts. Transcriptome analysis of JQ1-treated dcSSc fibroblasts revealed differentially expressed genes related to extracellular matrix, cell cycle, and calcium (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ) signaling. The antifibrotic effect of BRD4 inhibition was mediated at least in part by downregulation of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \/calmodulin\u2013dependent protein kinase II\n                    <jats:bold>\u03b1<\/jats:bold>\n                    and reduction of intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    concentrations. On the basis of these results, we propose targeting Ca\n                    <jats:sup>2+<\/jats:sup>\n                    pathways or BRD4 as potentially novel therapeutic approaches for progressive tissue fibrosis.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.150871","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T12:01:51Z","timestamp":1648555311000},"source":"Crossref","is-referenced-by-count":28,"title":["Inhibition of bromodomain extraterminal histone readers alleviates skin fibrosis in experimental models of scleroderma"],"prefix":"10.1172","volume":"7","author":[{"given":"Sirapa","family":"Vichaikul","sequence":"first","affiliation":[{"name":"Division of Rheumatology and Clinical Autoimmunity Center of Excellence, Department of Internal Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0478-1751","authenticated-orcid":true,"given":"Mikel","family":"Gurrea-Rubio","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Autoimmunity Center of Excellence, Department of Internal Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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