{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T02:23:30Z","timestamp":1767666210211,"version":"3.41.2"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Sarcoidosis is a systemic granulomatous disease of unknown cause. Natural improvement with favorable outcome is common, but a significant number of patients present with difficult to manage and progressive disease. The identification of biomarkers associated with disease activity and progression is warranted. Extracellular heat shock protein 90 (HSP90) <jats:italic>\u03b1<\/jats:italic> is a signaling molecule released by cells that induces proinflammatory signaling through interaction with certain receptors, such as lipoprotein receptor\u2013related protein 1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>HSP90\u03b1 protein expression in lung tissues derived from patients diagnosed with sarcoidosis and control subjects was assessed by immunohistochemistry. Serum HSP90\u03b1 concentration was measured in sarcoidosis patients and healthy controls and correlated with clinical outcomes. Bronchoalveolar lavage fluid (BALF) was collected and analyzed for HSP90\u03b1 expression. Extracellular HSP90\u03b1 released from macrophages was examined in human primary cells and an immortalized cell line.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Macrophages and granulomas in sarcoidosis-affected lungs showed high HSP90\u03b1 expression. Serum HSP90\u03b1 levels were elevated in sarcoidosis patients compared with controls and correlated with BALF HSP90\u03b1 levels. HSP90\u03b1 concentrations in the circulation were correlated with biomarkers of disease stage. Both primary and immortalized macrophages showed a high capacity for secreting extracellular HSP90\u03b1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results demonstrate that macrophages in the lungs of sarcoidosis patients produce high levels of HSP90\u03b1, suggesting HSP90\u03b1 as a potential biomarker and therapeutic target.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1532437","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T05:10:29Z","timestamp":1736917829000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Upregulation of HSP90\u03b1 in the lungs and circulation in sarcoidosis"],"prefix":"10.3389","volume":"12","author":[{"given":"Takuma","family":"Isshiki","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motoko","family":"Sunakawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan","family":"Vierhout","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anmar","family":"Ayoub","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pareesa","family":"Ali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Safaa","family":"Naiel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shion","family":"Miyoshi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asghar","family":"Naqvi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan","family":"Hambly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuma","family":"Kishi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kjetil","family":"Ask","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin R. 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