{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:37:00Z","timestamp":1771461420265,"version":"3.50.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100010198","name":"Ministerio de Asuntos Econ\u00f3micos y Transformaci\u00f3n Digital, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["RTI2018-095214-B-I00"],"award-info":[{"award-number":["RTI2018-095214-B-I00"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Ministerio de Asuntos Econ\u00f3micos y Transformaci\u00f3n Digital, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["SAF2016-75195-R"],"award-info":[{"award-number":["SAF2016-75195-R"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Ministerio de Asuntos Econ\u00f3micos y Transformaci\u00f3n Digital, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["SAF2017-82905-R"],"award-info":[{"award-number":["SAF2017-82905-R"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Systemic sclerosis (SSc) is an autoimmune disease that affects skin and multiple internal organs. TGF-\u03b2, a central trigger of cutaneous fibrosis, activates fibroblasts with the involvement of the stress-inducible chaperone heat shock protein 90 isoform \u03b1 (Hsp90\u03b1). Available evidence supports overexpression and secretion of Hsp90\u03b1 as a feature in profibrotic pathological conditions. The aim of this work is to investigate the expression and function of Hsp90\u03b1 in experimental models of skin fibrosis such as human fibroblasts, C57BL\/6 mice, and in human SSc. For this purpose, we generated a new experimental model based on doxorubicin administration with improved characteristics with respect to the bleomycin model. We visualized disease progression in vivo by fluorescence imaging. In this work, we obtained Hsp90\u03b1 mRNA overexpression in human skin fibroblasts, in bleomycin- and doxorubicin-induced mouse fibrotic skin, and in lungs of bleomycin- and doxorubicin-treated mice. Hsp90\u03b1-deficient mice showed significantly decreased skin thickness compared with wild-type mice in both animal models. In SSc patients, serum Hsp90\u03b1 levels were increased in patients with lung involvement and in patients with the diffuse form of SSc (dSSc) compared with patients with the limited form of SSc. The serum Hsp90\u03b1 levels of patients dSSc were correlated with the Rodnan score and the forced vital capacity variable. These results provide new supportive evidence of the contribution of the Hsp90\u03b1 isoform in the development of skin fibrosis. In SSc, these results indicated that higher serum levels were associated with dSSc and lung fibrosis.<\/jats:p>","DOI":"10.4049\/jimmunol.2100430","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T19:13:32Z","timestamp":1657739612000},"page":"38-48","source":"Crossref","is-referenced-by-count":4,"title":["Profibrotic Role of Inducible Heat Shock Protein 90\u03b1 Isoform in Systemic Sclerosis"],"prefix":"10.1093","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4959-8181","authenticated-orcid":false,"given":"Jorge","family":"RuizdelRio","sequence":"first","affiliation":[{"name":"Instituto de Biomedicina y Biotecnolog\u00eda de Cantabria, Consejo Superior de Investigaciones Cient\u00edficas\u2013Universidad de Cantabria , Santander,","place":["Spain"]},{"name":"Instituto de Investigaci\u00f3n Marqu\u00e9s de Valdecilla (IDIVAL) , Santander,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Gerencia Atenci\u00f3n Primaria, Servicio C\u00e1ntabro de Salud , Santander,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8279-3806","authenticated-orcid":false,"given":"Patricia","family":"Carreira","sequence":"additional","affiliation":[{"name":"Servicio de Reumatolog\u00eda, Instituto de Investigaci\u00f3n Hospital 12 de Octubre (i+12) , Madrid,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Maestro","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina y Biotecnolog\u00eda de Cantabria, Consejo Superior de Investigaciones Cient\u00edficas\u2013Universidad de Cantabria , Santander,","place":["Spain"]},{"name":"Instituto de Investigaci\u00f3n Marqu\u00e9s de Valdecilla (IDIVAL) , Santander,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7229-6005","authenticated-orcid":false,"given":"Jose L","family":"Pablos","sequence":"additional","affiliation":[{"name":"Servicio de Reumatolog\u00eda, Instituto de Investigaci\u00f3n Hospital 12 de Octubre (i+12) , Madrid,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7274-7021","authenticated-orcid":false,"given":"Ana","family":"Palanca","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Marqu\u00e9s de Valdecilla (IDIVAL) , Santander,","place":["Spain"]},{"name":"Departamento de Anatom\u00eda y Biolog\u00eda Celular, Universidad de Cantabria , Santander,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3476-1150","authenticated-orcid":false,"given":"Jesus","family":"Merino","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Marqu\u00e9s de Valdecilla (IDIVAL) , Santander,","place":["Spain"]},{"name":"Departamento de Biolog\u00eda Molecular, Universidad de Cantabria , Santander,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4990-8162","authenticated-orcid":false,"given":"Anna","family":"Serrano-Mollar","sequence":"additional","affiliation":[{"name":"Departamento de Patolog\u00eda Experimental, Instituto de Investigaciones Biom\u00e9dicas de Barcelona (IIBB-CSIC-IDIBAPS) , Barcelona,","place":["Spain"]},{"name":"Centro de Investigaciones Biom\u00e9dicas en Red de Enfermedades Respiratorias , Madrid,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramon","family":"Merino","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina y Biotecnolog\u00eda de Cantabria, Consejo Superior de Investigaciones Cient\u00edficas\u2013Universidad de Cantabria , Santander,","place":["Spain"]},{"name":"Departamento de Biolog\u00eda Molecular, Universidad de Cantabria , Santander,","place":["Spain"]},{"name":"SODERCAN , Santander,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6854-052X","authenticated-orcid":false,"given":"Esther","family":"Tamayo","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Molecular, Universidad de Cantabria , Santander,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0562-427X","authenticated-orcid":false,"given":"Marcos","family":"Lopez-Hoyos","sequence":"additional","affiliation":[{"name":"Servicio de Inmunolog\u00eda, Hospital Universitario Marqu\u00e9s de Valdecilla , Santander,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Diaz-Gonzalez","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad de La Laguna, Servicio de Reumatolog\u00eda, Hospital Universitario de Canarias , La Laguna, Santa Cruz de Tenerife,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2916-8491","authenticated-orcid":false,"given":"Victor","family":"Martinez-Taboada","sequence":"additional","affiliation":[{"name":"Servicio de Reumatolog\u00eda, Hospital Universitario Marqu\u00e9s de Valdecilla, IDIVAL, Facultad de Medicina, Universidad de Cantabria , Santander,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4588-9598","authenticated-orcid":false,"given":"Ana V","family":"Villar","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina y Biotecnolog\u00eda de Cantabria, Consejo Superior de Investigaciones Cient\u00edficas\u2013Universidad de Cantabria , Santander,","place":["Spain"]},{"name":"Instituto de Investigaci\u00f3n Marqu\u00e9s de Valdecilla (IDIVAL) , Santander,","place":["Spain"]},{"name":"Departamento de Fisiolog\u00eda y Farmacolog\u00eda, Universidad de Cantabria , Santander,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,7,1]]},"reference":[{"key":"2025021008181724700_r1","doi-asserted-by":"crossref","first-page":"e000782","DOI":"10.1136\/rmdopen-2018-000782","article-title":"Systemic sclerosis: state of the 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