Upregulation of HSP90α in the lungs and circulation in sarcoidosis
BackgroundSarcoidosis 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 progr...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2025.1532437/full |
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| author | Takuma Isshiki Takuma Isshiki Takuma Isshiki Motoko Sunakawa Megan Vierhout Megan Vierhout Anmar Ayoub Anmar Ayoub Pareesa Ali Pareesa Ali Safaa Naiel Safaa Naiel Shion Miyoshi Asghar Naqvi Nathan Hambly Kazuma Kishi Kjetil Ask Kjetil Ask Martin R. J. Kolb |
| author_facet | Takuma Isshiki Takuma Isshiki Takuma Isshiki Motoko Sunakawa Megan Vierhout Megan Vierhout Anmar Ayoub Anmar Ayoub Pareesa Ali Pareesa Ali Safaa Naiel Safaa Naiel Shion Miyoshi Asghar Naqvi Nathan Hambly Kazuma Kishi Kjetil Ask Kjetil Ask Martin R. J. Kolb |
| author_sort | Takuma Isshiki |
| collection | DOAJ |
| description | BackgroundSarcoidosis 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) α is a signaling molecule released by cells that induces proinflammatory signaling through interaction with certain receptors, such as lipoprotein receptor–related protein 1.Materials and methodsHSP90α protein expression in lung tissues derived from patients diagnosed with sarcoidosis and control subjects was assessed by immunohistochemistry. Serum HSP90α concentration was measured in sarcoidosis patients and healthy controls and correlated with clinical outcomes. Bronchoalveolar lavage fluid (BALF) was collected and analyzed for HSP90α expression. Extracellular HSP90α released from macrophages was examined in human primary cells and an immortalized cell line.ResultsMacrophages and granulomas in sarcoidosis-affected lungs showed high HSP90α expression. Serum HSP90α levels were elevated in sarcoidosis patients compared with controls and correlated with BALF HSP90α levels. HSP90α concentrations in the circulation were correlated with biomarkers of disease stage. Both primary and immortalized macrophages showed a high capacity for secreting extracellular HSP90α.ConclusionThese results demonstrate that macrophages in the lungs of sarcoidosis patients produce high levels of HSP90α, suggesting HSP90α as a potential biomarker and therapeutic target. |
| format | Article |
| id | doaj-art-4c4eb2385b3d4fb494b9cfc313e8ceee |
| institution | Kabale University |
| issn | 2296-858X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj-art-4c4eb2385b3d4fb494b9cfc313e8ceee2025-01-15T05:10:23ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-01-011210.3389/fmed.2025.15324371532437Upregulation of HSP90α in the lungs and circulation in sarcoidosisTakuma Isshiki0Takuma Isshiki1Takuma Isshiki2Motoko Sunakawa3Megan Vierhout4Megan Vierhout5Anmar Ayoub6Anmar Ayoub7Pareesa Ali8Pareesa Ali9Safaa Naiel10Safaa Naiel11Shion Miyoshi12Asghar Naqvi13Nathan Hambly14Kazuma Kishi15Kjetil Ask16Kjetil Ask17Martin R. J. Kolb18Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON, CanadaDepartment of Pathology and Molecular Medicine, McMaster Immunology Research Center, McMaster University, Hamilton, ON, CanadaDepartment of Respiratory Medicine, Toho University School of Medicine, Tokyo, JapanDepartment of Respiratory Medicine, Toho University School of Medicine, Tokyo, JapanDepartment of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON, CanadaDepartment of Pathology and Molecular Medicine, McMaster Immunology Research Center, McMaster University, Hamilton, ON, CanadaDepartment of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON, CanadaDepartment of Pathology and Molecular Medicine, McMaster Immunology Research Center, McMaster University, Hamilton, ON, CanadaDepartment of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON, CanadaDepartment of Pathology and Molecular Medicine, McMaster Immunology Research Center, McMaster University, Hamilton, ON, CanadaDepartment of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON, CanadaDepartment of Pathology and Molecular Medicine, McMaster Immunology Research Center, McMaster University, Hamilton, ON, CanadaDepartment of Respiratory Medicine, Toho University School of Medicine, Tokyo, JapanDepartment of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON, CanadaDepartment of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON, CanadaDepartment of Respiratory Medicine, Toho University School of Medicine, Tokyo, JapanDepartment of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON, CanadaDepartment of Pathology and Molecular Medicine, McMaster Immunology Research Center, McMaster University, Hamilton, ON, CanadaDepartment of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON, CanadaBackgroundSarcoidosis 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) α is a signaling molecule released by cells that induces proinflammatory signaling through interaction with certain receptors, such as lipoprotein receptor–related protein 1.Materials and methodsHSP90α protein expression in lung tissues derived from patients diagnosed with sarcoidosis and control subjects was assessed by immunohistochemistry. Serum HSP90α concentration was measured in sarcoidosis patients and healthy controls and correlated with clinical outcomes. Bronchoalveolar lavage fluid (BALF) was collected and analyzed for HSP90α expression. Extracellular HSP90α released from macrophages was examined in human primary cells and an immortalized cell line.ResultsMacrophages and granulomas in sarcoidosis-affected lungs showed high HSP90α expression. Serum HSP90α levels were elevated in sarcoidosis patients compared with controls and correlated with BALF HSP90α levels. HSP90α concentrations in the circulation were correlated with biomarkers of disease stage. Both primary and immortalized macrophages showed a high capacity for secreting extracellular HSP90α.ConclusionThese results demonstrate that macrophages in the lungs of sarcoidosis patients produce high levels of HSP90α, suggesting HSP90α as a potential biomarker and therapeutic target.https://www.frontiersin.org/articles/10.3389/fmed.2025.1532437/fullsarcoidosisgranulomaHsp90αextracellular Hsp90αbiomarker |
| spellingShingle | Takuma Isshiki Takuma Isshiki Takuma Isshiki Motoko Sunakawa Megan Vierhout Megan Vierhout Anmar Ayoub Anmar Ayoub Pareesa Ali Pareesa Ali Safaa Naiel Safaa Naiel Shion Miyoshi Asghar Naqvi Nathan Hambly Kazuma Kishi Kjetil Ask Kjetil Ask Martin R. J. Kolb Upregulation of HSP90α in the lungs and circulation in sarcoidosis Frontiers in Medicine sarcoidosis granuloma Hsp90α extracellular Hsp90α biomarker |
| title | Upregulation of HSP90α in the lungs and circulation in sarcoidosis |
| title_full | Upregulation of HSP90α in the lungs and circulation in sarcoidosis |
| title_fullStr | Upregulation of HSP90α in the lungs and circulation in sarcoidosis |
| title_full_unstemmed | Upregulation of HSP90α in the lungs and circulation in sarcoidosis |
| title_short | Upregulation of HSP90α in the lungs and circulation in sarcoidosis |
| title_sort | upregulation of hsp90α in the lungs and circulation in sarcoidosis |
| topic | sarcoidosis granuloma Hsp90α extracellular Hsp90α biomarker |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2025.1532437/full |
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