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Oncostatin M, a member of the IL-6 family, is elevated in SSc serum and was recognized as a significant player in various stages of fibrosis. The goal of this study was to assess the contribution of the OSM\/OSMR\u03b2 pathway to endothelial cell (EC) injury and activation in SSc.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      IHC and IF were used to assess the distribution of OSM and OSMR\u03b2 in SSc (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200914) and healthy control (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20097) skin biopsies. Cell culture experiments were performed in human dermal microvascular endothelial cells (HDMECs) and included mRNA and protein analysis, and cell migration and proliferation assays. Ex vivo skin organoid culture was used to evaluate the effect of OSM on perivascular fibrosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      OSMR\u03b2 protein was elevated in dermal ECs and in fibroblasts of SSc patients. Treatments of HDMECs with OSM or IL-6+sIL-6R have demonstrated that both cytokines similarly stimulated proinflammatory genes and genes related to endothelial to mesenchymal transition (EndMT). OSM was more effective than IL-6+sIL-6R in inducing cell migration, while both treatments similarly induced cell proliferation. The effects of OSM were mediated via OSMR\u03b2 and STAT3, while the LIFR did not contribute to these responses. Both OSM and IL-6+sIL-6R induced profibrotic gene expression in HDMECs, as well as expansion of the perivascular PDGFR\u03b2\n                      <jats:sup>+<\/jats:sup>\n                      cells in the ex vivo human skin culture system. Additional studies in HDMECs showed that siRNA-mediated downregulation of FLI1 and its close homolog ERG resulted in increased expression of OSMR\u03b2 in HDMECs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This work provides new insights into the role of the OSM\/OSMR\u03b2 axis in activation\/injury of dermal ECs and supports the involvement of this pathway in SSc vascular disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13075-020-02266-0","type":"journal-article","created":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T06:03:45Z","timestamp":1596175425000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["The role of the oncostatin M\/OSM receptor \u03b2 axis in activating dermal microvascular endothelial cells in systemic sclerosis"],"prefix":"10.1186","volume":"22","author":[{"given":"G.","family":"Marden","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q.","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Wilks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Nevin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Feeney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Wisniacki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Trojanowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Bujor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Stawski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9550-7178","authenticated-orcid":false,"given":"M.","family":"Trojanowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,31]]},"reference":[{"issue":"3","key":"2266_CR1","doi-asserted-by":"publisher","first-page":"137","DOI":"10.5301\/jsrd.5000249","volume":"2","author":"J Varga","year":"2017","unstructured":"Varga J, Trojanowska M, Kuwana M. 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