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Cultured SSc fibrocytes were maintained in growth medium (untreated cells) or treated with nintedanib 0.1 and 1\u2009\u03bcM for 3 and 24\u2009h. Fibroblast-specific protein-1 (S100A4) and \u03b1-smooth muscle actin (\u03b1SMA), as markers of fibroblast\/myofibroblast phenotype, together with type I collagen (COL1) and fibronectin (FN), were investigated by qRT-PCR and Western blotting. Non-parametric tests were used for statistical analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Significantly elevated gene and protein expressions of \u03b1SMA, S100A4, COL1, and FN were observed in SSc fibrocytes compared to HS fibrocytes (gene: \u03b1SMA\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001; others\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.0001; protein: all\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05). Interestingly, an increased gene and protein expression of \u03b1SMA and S100A4 was found in fibrocytes from SSc patients positive for anti-Scl70 and with interstitial lung disease (ILD) (Scl70\n                      <jats:sup>+<\/jats:sup>\n                      ILD\n                      <jats:sup>+<\/jats:sup>\n                      ) compared to Scl70\n                      <jats:sup>\u2212<\/jats:sup>\n                      ILD\n                      <jats:sup>\u2212<\/jats:sup>\n                      patients (S100A4: gene:\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.01; protein:\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05), whereas no differences were observed for COL1 and FN.\n                    <\/jats:p>\n                    <jats:p>Nintedanib reduced gene and protein expression of \u03b1SMA, S100A4, COL1, and FN in SSc fibrocytes compared to untreated ones with different statistical significance.<\/jats:p>\n                    <jats:p>\n                      Noteworthy, nintedanib significantly downregulated gene and protein expression of \u03b1SMA, S100A4, COL1, and FN in Scl70\n                      <jats:sup>+<\/jats:sup>\n                      ILD\n                      <jats:sup>+<\/jats:sup>\n                      fibrocytes (all\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05), whereas only that of S100A4 and FN was significantly downregulated (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05) in Scl70\n                      <jats:sup>\u2212<\/jats:sup>\n                      ILD\n                      <jats:sup>\u2212<\/jats:sup>\n                      fibrocytes compared to the related untreated cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Nintedanib seems to downregulate in vitro the transition of fibrocytes into myofibroblasts and their pro-fibrotic activity, particularly in cells isolated from Scl70\n                      <jats:sup>+<\/jats:sup>\n                      ILD\n                      <jats:sup>+<\/jats:sup>\n                      SSc patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13075-021-02555-2","type":"journal-article","created":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T06:02:58Z","timestamp":1627970578000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Nintedanib downregulates the transition of cultured systemic sclerosis fibrocytes into myofibroblasts and their pro-fibrotic activity"],"prefix":"10.1186","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5396-0932","authenticated-orcid":false,"given":"Maurizio","family":"Cutolo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Gotelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Montagna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuele","family":"Tardito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Paolino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Pizzorni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Sulli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Soldano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,3]]},"reference":[{"issue":"7","key":"2555_CR1","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1080\/1744666X.2019.1614915","volume":"15","author":"M Cutolo","year":"2019","unstructured":"Cutolo M, Soldano S, Smith V. 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