{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T22:07:31Z","timestamp":1784758051754,"version":"3.55.0"},"reference-count":56,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100015661","name":"UCB Pharma","doi-asserted-by":"publisher","award":["21856"],"award-info":[{"award-number":["21856"]}],"id":[{"id":"10.13039\/100015661","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":[[2025,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Scleroderma is a life\u2010threatening autoimmune disease characterized by inflammation, tissue remodeling, and fibrosis. This study aimed to investigate the expression and function of transglutaminase 2 (TGM2) in scleroderma skin and experimentally induced dermal fibrosis to determine its potential role and therapeutic implications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed immunohistochemistry on skin sections to assess TGM2 expression and localization, and protein biochemistry of both systemic sclerosis\u2013derived and healthy control dermal fibroblasts to assess TGM2 expression, function, and extracellular matrix deposition in the presence of TGM2 inhibiting and transforming growth factor (TGF)\u2010\u03b2 neutralizing antibodies and a small\u2010molecule inhibitor of the TGF\u2010\u03b2RI kinase. Mice with a complete deficiency of TGM2 (\n                      <jats:italic>Tgm2\u2010\/\u2010)<\/jats:italic>\n                      were investigated in the bleomycin\u2010induced model of skin fibrosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TGM2 was found to be widely expressed in both control and scleroderma skin samples, as well as in cultured fibroblasts. Scleroderma fibroblasts exhibited elevated TGM2 expression, which correlated with increased expression of fibrosis markers (Col\u20101, \u03b1SMA, and CCN2). Inhibition of TGM2 using an inhibiting antibody reduced the expression of key markers of fibrosis. The effects of TGM2 inhibition were similar to those observed with TGF\u2010\u03b2 neutralization, suggesting a potential crosstalk between TGM2 and TGF\u2010\u03b2 signaling. Moreover,\n                      <jats:italic>TGM2<\/jats:italic>\n                      knockout mice showed significantly reduced dermal fibrosis compared with wild type mice. In vitro experiments with\n                      <jats:italic>TGM2<\/jats:italic>\n                      \u2010deleted fibroblasts demonstrated impaired cell migration and collagen matrix contraction, which could be partially restored by exogenous TGF\u2010\u03b2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TGM2 can regulate several key profibrotic activities of TGF\u2010\u03b2 suggesting that attenuating TGM2 function may be of benefit in severe forms of connective tissue disease with skin fibrosis.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art43104-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.43104","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:49:41Z","timestamp":1736729381000},"page":"914-928","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Critical Role for Transglutaminase 2 in Scleroderma Skin Fibrosis and in the Development of Dermal Sclerosis in a Mouse Model of Scleroderma"],"prefix":"10.1002","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0244-0109","authenticated-orcid":false,"given":"Angela Y. 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