The role of heat shock protein 90 in idiopathic pulmonary fibrosis: state of the art

Heat shock protein 90 (HSP 90) and its isoforms are a group of homodimeric proteins that regulate several cellular processes, such as the elimination of misfolded proteins, cell development and post-translational modifications of kinase proteins and receptors. Due to its involvement in extracellular...

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Main Authors: Giorgio Monteleone, Paolo Cameli, Francesco Bonella
Format: Article
Language:English
Published: European Respiratory Society 2025-03-01
Series:European Respiratory Review
Online Access:http://err.ersjournals.com/content/34/175/240147.full
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author Giorgio Monteleone
Paolo Cameli
Francesco Bonella
author_facet Giorgio Monteleone
Paolo Cameli
Francesco Bonella
author_sort Giorgio Monteleone
collection DOAJ
description Heat shock protein 90 (HSP 90) and its isoforms are a group of homodimeric proteins that regulate several cellular processes, such as the elimination of misfolded proteins, cell development and post-translational modifications of kinase proteins and receptors. Due to its involvement in extracellular matrix (ECM) remodelling, myofibroblast differentiation and apoptosis, HSP 90 has been investigated as a key player in the pathogenesis of lung fibrosis. Idiopathic pulmonary fibrosis (IPF) is the most common and deadly interstitial lung disease, due to the progressive distortion of lung parenchyma related to the overproduction and deposition of altered ECM, driven by transforming growth factor-β (TGF-β) dependent and independent pathways. The inhibition or induction of HSP 90 is associated with a reduced or increased expression of TGF-β receptors, respectively, suggesting a role for HSP 90 as a biomarker and therapeutic target in IPF. Experimental drugs such as geldanamycin and its derivatives 17-AAG (17-N-allylamino-17-demethoxygeldanamicin) and 17-DMAG (17-dimethylaminoethylamino-17-demethoxigeldanamycin), along with AUY-922, 1G6-D7, AT-13387, TAS-116 and myricetin, have been found to reduce lung fibrosis in both in vivo and in vitro models, supporting the role of this emerging target. This review aims to illustrate the structure and biological function of HSP 90 in the context of IPF pathobiology, as well as perspective application of this molecule as a biomarker and therapeutic target for IPF.
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spelling doaj-art-dddbcecd325a4183b818e6e696e2d97d2025-08-20T03:40:57ZengEuropean Respiratory SocietyEuropean Respiratory Review0905-91801600-06172025-03-013417510.1183/16000617.0147-20240147-2024The role of heat shock protein 90 in idiopathic pulmonary fibrosis: state of the artGiorgio Monteleone0Paolo Cameli1Francesco Bonella2 Department of Cardiovascular and Pulmonary Sciences, Catholic University of Sacred Heart, Rome, Italy Respiratory Diseases Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy Center for interstitial and rare lung diseases, Pneumology Department, Ruhrlandklinik University Hospital, University of Duisburg-Essen, Essen, Germany Heat shock protein 90 (HSP 90) and its isoforms are a group of homodimeric proteins that regulate several cellular processes, such as the elimination of misfolded proteins, cell development and post-translational modifications of kinase proteins and receptors. Due to its involvement in extracellular matrix (ECM) remodelling, myofibroblast differentiation and apoptosis, HSP 90 has been investigated as a key player in the pathogenesis of lung fibrosis. Idiopathic pulmonary fibrosis (IPF) is the most common and deadly interstitial lung disease, due to the progressive distortion of lung parenchyma related to the overproduction and deposition of altered ECM, driven by transforming growth factor-β (TGF-β) dependent and independent pathways. The inhibition or induction of HSP 90 is associated with a reduced or increased expression of TGF-β receptors, respectively, suggesting a role for HSP 90 as a biomarker and therapeutic target in IPF. Experimental drugs such as geldanamycin and its derivatives 17-AAG (17-N-allylamino-17-demethoxygeldanamicin) and 17-DMAG (17-dimethylaminoethylamino-17-demethoxigeldanamycin), along with AUY-922, 1G6-D7, AT-13387, TAS-116 and myricetin, have been found to reduce lung fibrosis in both in vivo and in vitro models, supporting the role of this emerging target. This review aims to illustrate the structure and biological function of HSP 90 in the context of IPF pathobiology, as well as perspective application of this molecule as a biomarker and therapeutic target for IPF.http://err.ersjournals.com/content/34/175/240147.full
spellingShingle Giorgio Monteleone
Paolo Cameli
Francesco Bonella
The role of heat shock protein 90 in idiopathic pulmonary fibrosis: state of the art
European Respiratory Review
title The role of heat shock protein 90 in idiopathic pulmonary fibrosis: state of the art
title_full The role of heat shock protein 90 in idiopathic pulmonary fibrosis: state of the art
title_fullStr The role of heat shock protein 90 in idiopathic pulmonary fibrosis: state of the art
title_full_unstemmed The role of heat shock protein 90 in idiopathic pulmonary fibrosis: state of the art
title_short The role of heat shock protein 90 in idiopathic pulmonary fibrosis: state of the art
title_sort role of heat shock protein 90 in idiopathic pulmonary fibrosis state of the art
url http://err.ersjournals.com/content/34/175/240147.full
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