{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:04:33Z","timestamp":1792109073262,"version":"4.4.0"},"reference-count":53,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T00:00:00Z","timestamp":1732665600000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004484","name":"Tehran University of Medical Sciences and Health Services","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004484","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Fibrosis is a principal sign of systemic sclerosis (SSc) which can affect several organs including the lung, heart, and dermis. Dermal fibroblasts of SSc patients are characterized by persistent and activated Ras and ERK1\/2 signaling which stimulates extreme collagen and extracellular matrix synthesis. Salirasib is a Ras inhibitor that competitively prevents the adherence of GTP\u2010bound Ras to the plasma membrane, that inhibits Ras signaling. This study intended to clarify whether salirasib can influence fibrotic mediators in SSc fibroblasts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      Dermal fibroblasts from 10 SSc patients were treated with salirasib in the presence of TGF\u2010\u03b21, and mRNA levels of H\u2010Ras and genes related to fibrosis, such as\n                      <jats:italic>COL1A1, COL1A2<\/jats:italic>\n                      ,\n                      <jats:italic>CTGF<\/jats:italic>\n                      ,\n                      <jats:italic>TGF\u2010\u03b21<\/jats:italic>\n                      , fibronectin,\n                      <jats:italic>ACTA2<\/jats:italic>\n                      , and\n                      <jats:italic>MMP1<\/jats:italic>\n                      was measured by real\u2010time PCR. The \u03b1\u2010SMA protein expression was analyzed by immunofluorescence staining.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In dermal fibroblasts of SSc patients, salirasib treatment, markedly downregulated the\n                      <jats:italic>H\u2010Ras<\/jats:italic>\n                      gene expression. In addition, the protein expression of \u03b1\u2010SMA and gene expression of\n                      <jats:italic>ACTA2<\/jats:italic>\n                      were inhibited upon salirasib treatment. Salirasib also significantly reduced the expression of\n                      <jats:italic>COL1A1<\/jats:italic>\n                      , and\n                      <jats:italic>COL1A2<\/jats:italic>\n                      genes and augmented the gene expression of\n                      <jats:italic>MMP1<\/jats:italic>\n                      . The mRNA levels of other genes related to fibrosis such as\n                      <jats:italic>FN1<\/jats:italic>\n                      ,\n                      <jats:italic>CTGF<\/jats:italic>\n                      , and\n                      <jats:italic>TGF\u2010\u03b21<\/jats:italic>\n                      were significantly decreased upon salirasib treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Considering salirasib significantly reduced the expression of genes related to the fibrosis process and \u03b1\u2010SMA gene and protein expression, and given significant upregulation of\n                      <jats:italic>MMP1<\/jats:italic>\n                      by salirasib, it can be considered as a new curative strategy for fibrotic diseases like SSc.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.70063","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T09:28:51Z","timestamp":1732699731000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Salirasib Inhibits the Expression of Genes Involved in Fibrosis in Fibroblasts of Systemic Sclerosis Patients"],"prefix":"10.1002","volume":"12","author":[{"given":"Mina","family":"Sadeghi Shaker","sequence":"first","affiliation":[{"name":"Department of Immunology, School of Medicine Tehran University of Medical Sciences Tehran Iran"},{"name":"Rheumatology Research Center Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohsen","family":"Rokni","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine Tehran University of Medical Sciences Tehran Iran"},{"name":"Rheumatology Research Center Tehran University of Medical Sciences Tehran Iran"},{"name":"Department of Immunology University of social Welfare and Rehabilitation Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4762-6943","authenticated-orcid":false,"given":"Hoda","family":"Kavosi","sequence":"additional","affiliation":[{"name":"Rheumatology Research Center Tehran University of Medical Sciences Tehran Iran"},{"name":"Research Center for Chronic Inflammatory Diseases Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samaneh","family":"Enayati","sequence":"additional","affiliation":[{"name":"Rheumatology Research Center Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham","family":"Madreseh","sequence":"additional","affiliation":[{"name":"Rheumatology Research Center Tehran University of Medical Sciences Tehran Iran"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8164-8831","authenticated-orcid":false,"given":"Mahdi","family":"Mahmoudi","sequence":"additional","affiliation":[{"name":"Rheumatology Research Center Tehran University of Medical Sciences Tehran Iran"},{"name":"Research Center for Chronic Inflammatory Diseases Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4324-2697","authenticated-orcid":false,"given":"Elham","family":"Farhadi","sequence":"additional","affiliation":[{"name":"Rheumatology Research Center Tehran University of Medical Sciences Tehran Iran"},{"name":"Research Center for Chronic Inflammatory Diseases Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Vodjgani","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,27]]},"reference":[{"key":"e_1_2_12_2_1","volume-title":"The Role of the Acquired Immune Response in Systemic Sclerosis. 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