{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T22:42:02Z","timestamp":1773441722551,"version":"3.50.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2019,1,4]],"date-time":"2019-01-04T00:00:00Z","timestamp":1546560000000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010482","name":"FRSR","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010482","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fonds de Recherche Scientifique en Rhumatologie"},{"name":"Fonds National de la Recherche Scientifique"},{"name":"Communaut\u00e9 fran\u00e7aise de Belgique"},{"name":"Association scl\u00e9rodermique de France"},{"DOI":"10.13039\/100001468","name":"ASF","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001468","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Ubiquitination of proteins leads to their degradation by the proteasome, and is regulated by ubiquitin ligases and substrate-specific ubiquitin-specific peptidases (USPs). The ubiquitination process also plays important roles in the regulation of cell metabolism and cell cycle. Here, we found that the expression of several USPs is increased in SSc tenosynovial and skin biopsies, and we demonstrated that USP inhibition decreases TGF-\u03b2 signalling in primary fibroblast cell lines.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>High-density transcriptomic studies were performed using total RNA obtained from SSc tenosynovial samples. Confirmatory immunostaining experiments were performed on tenosynovial and skin samples. In vitro experiments were conducted in order to study the influence of USP modulation on responses to TGF-\u03b2 stimulation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Tenosynovial biopsies from SSc patients overexpressed known disease-associated gene pathways: fibrosis, cytokines and chemokines, and Wnt\/TGF-\u03b2 signalling, but also several USPs. Immunohistochemistry experiments confirmed the detection of USPs in the same samples, and in SSc skin biopsies. Exposure of primary fibroblast cell lines to TGF-\u03b2 induced USP gene expression. The use of a pan-USP inhibitor decreased SMAD3 phosphorylation, and expression of COL1A1, COL3A1 and fibronectin gene expression in TGF-\u03b2-stimulated fibroblasts. The effect of the USP inhibitor resulted in increased SMAD3 ubiquitination, and was blocked by a proteasome inhibitor, thereby confirming the specificity of its action.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Overexpression of several USPs, including USP15, amplifies fibrotic responses induced by TGF-\u03b2, and is a potential therapeutic target in SSc.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/rheumatology\/key401","type":"journal-article","created":{"date-parts":[[2018,11,27]],"date-time":"2018-11-27T15:12:26Z","timestamp":1543331546000},"page":"708-718","source":"Crossref","is-referenced-by-count":16,"title":["Overexpression of ubiquitin-specific peptidase 15 in systemic sclerosis fibroblasts increases response to transforming growth factor \u03b2"],"prefix":"10.1093","volume":"58","author":[{"given":"Christine","family":"Galant","sequence":"first","affiliation":[{"name":"P\u00f4le de Pathologies Rhumatismales Inflammatoires et Syst\u00e9miques, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 catholique de Louvain, Belgium"},{"name":"Department of Pathology, Cliniques Universitaires Saint-Luc, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel","family":"Marchandise","sequence":"additional","affiliation":[{"name":"P\u00f4le de Pathologies Rhumatismales Inflammatoires et Syst\u00e9miques, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 catholique de Louvain, Belgium"},{"name":"Department of Pathology, Cliniques Universitaires Saint-Luc, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria S","family":"Stoenoiu","sequence":"additional","affiliation":[{"name":"P\u00f4le de Pathologies Rhumatismales Inflammatoires et Syst\u00e9miques, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 catholique de Louvain, Belgium"},{"name":"Department of Rheumatology, Cliniques Universitaires Saint-Luc, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Ducreux","sequence":"additional","affiliation":[{"name":"P\u00f4le de Pathologies Rhumatismales Inflammatoires et Syst\u00e9miques, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 catholique de Louvain, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aur\u00e9lie","family":"De Groof","sequence":"additional","affiliation":[{"name":"P\u00f4le de Pathologies Rhumatismales Inflammatoires et Syst\u00e9miques, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 catholique de Louvain, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Pirenne","sequence":"additional","affiliation":[{"name":"Department of Pathology, Cliniques Universitaires Saint-Luc, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benoit","family":"Van den Eynde","sequence":"additional","affiliation":[{"name":"Institut de Duve, Department of Cancer Immunology and Immunotherapy, Universit\u00e9 catholique de Louvain, Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9ric A","family":"Houssiau","sequence":"additional","affiliation":[{"name":"P\u00f4le de Pathologies Rhumatismales Inflammatoires et Syst\u00e9miques, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 catholique de Louvain, Belgium"},{"name":"Department of Rheumatology, Cliniques Universitaires Saint-Luc, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard R","family":"Lauwerys","sequence":"additional","affiliation":[{"name":"P\u00f4le de Pathologies Rhumatismales Inflammatoires et Syst\u00e9miques, Institut de Recherche Exp\u00e9rimentale 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