{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:17:04Z","timestamp":1792016224879,"version":"4.4.0"},"reference-count":38,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T00:00:00Z","timestamp":1692144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21\u2010AR\u2010073947"],"award-info":[{"award-number":["R21\u2010AR\u2010073947"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001844","name":"Scleroderma Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001844","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Transport and Golgi Organization protein 1 (TANGO1) is a protein that regulates the export of procollagen from the endoplasmic reticulum and has a role in the organization of exit sites for general protein export. What regulates the expression of TANGO1 and the role of TANGO1 in fibrosis is poorly understood and has never been studied in the setting of systemic sclerosis (SSc). We undertook this study to determine the role of TANGO1 in SSc fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>SSc (n\u00a0=\u00a015) and healthy (n\u00a0=\u00a012) primary fibroblast lung cell lines were investigated for the expression of TANGO1. Histologic analyses for TANGO1 were performed on lung biopsy samples (n\u00a0=\u00a012 SSc patient samples and n\u00a0=\u00a08 healthy control samples).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SSc fibroblasts showed increased expression of TANGO1 protein in cultured fibroblasts. TANGO1 colocalizes with \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA)\u2013positive cells in SSc lung tissue and is highly up\u2010regulated in the neointima of SSc vessels. TANGO1 expression was dependent on the inflammasome activation of caspase 1. It was also dependent on signaling from the interleukin\u20101 (IL\u20101) and transforming growth factor \u03b2 (TGF\u03b2) receptors. The decrease in TANGO1 down\u2010regulated export of larger cargos including collagen and laminin. Reduced TANGO1 protein had no effect on smaller molecular weight cargoes; however, the secretion of elastin was significantly reduced.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>TANGO1 is markedly increased in SSc fibroblasts and was found to be elevated in lung tissue in association with \u03b1\u2010SMA\u2013positive cells. TANGO1 expression is driven by inflammasome\u2010dependent caspase 1 activation and is mediated by IL\u20101 and TGF\u03b2 downstream signaling. These observations suggest that during fibrosis, caspase 1 promotes the up\u2010regulation of TANGO1 and the organization of endoplasmic reticulum exits sites, ultimately contributing to procollagen export and fibrosis.<\/jats:p><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art42535-toc-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42535","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T10:39:10Z","timestamp":1681727950000},"page":"1831-1841","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Caspase 1 Enhances Transport and Golgi Organization Protein 1 Expression to Promote Procollagen Export From the Endoplasmic Reticulum in Systemic Sclerosis Contributing to Fibrosis"],"prefix":"10.1002","volume":"75","author":[{"given":"Lianne M.","family":"Connolly","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology Drexel University College of Medicine  Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caya M.","family":"McFalls","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Drexel University College of Medicine  Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle G.","family":"McMahon","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Drexel University College of Medicine  Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3744-3174","authenticated-orcid":false,"given":"Akash 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