{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T08:41:34Z","timestamp":1793695294699,"version":"4.5.1"},"reference-count":35,"publisher":"European Respiratory Society (ERS)","issue":"2","funder":[{"DOI":"10.13039\/501100000028","name":"Institute of Circulatory and Respiratory Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000028","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fonds de Dotation \"Recherche en Sant\u00e9 Respiratoire\" et de la Fondation du Souffle"},{"DOI":"10.13039\/100003284","name":"Pulmonary Fibrosis Foundation","doi-asserted-by":"publisher","award":["I.M. Rosenzweig Junior Investigator Award"],"award-info":[{"award-number":["I.M. 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We sought to study the role of heat shock protein (HSP) isoforms HSP90\u03b1 and HSP90\u03b2, whose distinct roles in lung fibrogenesis remain elusive.<\/jats:p><jats:p>We determined the level of circulating HSP90\u03b1 in IPF patients (n=31) and age-matched healthy controls (n=9) by ELISA. The release of HSP90\u03b1 and HSP90\u03b2 was evaluated<jats:italic>in vitro<\/jats:italic>in primary IPF and control lung fibroblasts and<jats:italic>ex vivo<\/jats:italic>after mechanical stretch on fibrotic lung slices from rats receiving adenovector-mediated transforming growth factor-\u03b21.<\/jats:p><jats:p>We demonstrate that circulating HSP90\u03b1 is upregulated in IPF patients in correlation with disease severity. The release of HSP90\u03b1 is enhanced by the increase in mechanical stress of the fibrotic ECM. This increase in extracellular HSP90\u03b1 signals through low-density lipoprotein receptor-related protein 1 (LRP1) to promote myofibroblast differentiation and persistence. In parallel, we demonstrate that the intracellular form of HSP90\u03b2 stabilises LRP1, thus amplifying HSP90\u03b1 extracellular action.<\/jats:p><jats:p>We believe that the specific inhibition of extracellular HSP90\u03b1 is a promising therapeutic strategy to reduce pro-fibrotic signalling in IPF.<\/jats:p>","DOI":"10.1183\/13993003.00386-2017","type":"journal-article","created":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T01:50:22Z","timestamp":1517449822000},"page":"1700386","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":56,"title":["Synergistic role of HSP90\u03b1 and HSP90\u03b2 to promote myofibroblast persistence in lung 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