{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T05:23:06Z","timestamp":1787721786551,"version":"build-2784847793"},"reference-count":43,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp;amp; Rheumatology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Dermal systemic sclerosis (SSc) fibroblasts and their exosomes can activate keratinocytes in SSc, with long noncoding RNA (lncRNA)\n                      <jats:italic>H19<\/jats:italic>\n                      highlighted as the most up\u2010regulated RNA in their cargo compared with healthy controls (HCs). The role of\n                      <jats:italic>H19<\/jats:italic>\n                      in SSc pathogenesis has never been investigated. Here we determine\n                      <jats:italic>H19<\/jats:italic>\n                      's role in the profibrotic activation of dermal fibroblasts and in their crosstalk with keratinocytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Skin biopsies were obtained from the forearms of patients with diffuse SSc (n\u00a0=\u00a020) or HCs (n\u00a0=\u00a08), and dermal fibroblasts were explanted. In situ hybridization was used to determine\n                      <jats:italic>H19<\/jats:italic>\n                      expression in the skin, paired with immunohistochemistry of STAT3 and Collagen1.\n                      <jats:italic>H19<\/jats:italic>\n                      and STAT3 expression were modulated by retroviral transduction and small interfering RNA. Gel contraction and Transwell coculture were employed for functional studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In SSc, high\n                      <jats:italic>H19<\/jats:italic>\n                      expression in skin and explanted dermal fibroblasts compared with HCs showed moderate correlation to well\u2010described profibrotic markers. Knockdown of\n                      <jats:italic>H19<\/jats:italic>\n                      in SSc fibroblasts decreased profibrotic gene expression and cell contraction ability.\n                      <jats:italic>H19<\/jats:italic>\n                      overexpression was sufficient to induce a profibrotic phenotype in HC fibroblasts. Mechanistically, transforming growth factor\u2010\u03b2, interleukin\u20106, and interleukin\u201011 significantly increased\n                      <jats:italic>H19<\/jats:italic>\n                      expression in HC fibroblasts (2.2\u2010, 1.4\u2010, and 3.5\u2010fold, respectively) through activation of STAT3. Additionally, the STAT3 and STAT1 activation of keratinocytes induced by coculture with SSc fibroblasts was suppressed by\n                      <jats:italic>H19<\/jats:italic>\n                      knockdown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study shows that lncRNA\n                      <jats:italic>H19<\/jats:italic>\n                      is a key mediator of STAT3\u2010induced changes in fibrotic activation of fibroblast and keratinocytes in SSc skin and could be considered a promising therapeutic target in tissue fibrosis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70104","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T19:28:16Z","timestamp":1772998096000},"page":"1929-1941","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Long Noncoding\n                    <scp>\n                      RNA\n                      <i>H19<\/i>\n                    <\/scp>\n                    Mediates\n                    <scp>STAT3<\/scp>\n                    \u2010Dependent Activation of Keratinocytes and Fibroblasts in Systemic Sclerosis Skin"],"prefix":"10.1002","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5278-5573","authenticated-orcid":false,"given":"Bego\u00f1a","family":"Caballero\u2010Ruiz","sequence":"first","affiliation":[{"name":"Leeds Institute of Rheumatic and Musculoskeletal Medicine University of Leeds  Leeds United 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