ArticleThe Journal of clinical investigation2019
HSP90 inhibitor geldanamycin reverts IL-13- and IL-17-induced airway goblet cell metaplasia.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 69 citations in OpenAlex.
- Toxic in vitro effects of flavoured-air inhalers containing essential oils in differentiated human nasal epithelial cells at air-liquid interface.Archives of toxicology · 2026Article
- Airway epithelial heterogeneity and mucus plugging in asthmatic bronchioles.American journal of respiratory and critical care medicine · 2026Article
- UPLC-Q-TOF-MS, Network Pharmacology and Molecular Docking to Reveal the Antidepressant Mechanism of the Different Components of Medicinal and Edible Lilies (Combinatorial chemistry & high throughput screening · 2026Article
- The Potential of Coenzyme Q10 in Alzheimer's Disease: Reducing IL-17 Induced Inflammation and Oxidative Stress for Neuroprotection.Current drug research reviews · 2026Review
- Porcine airway tissue explant culture at a hydrogel-air interface to model submucosal glands in cystic fibrosis progression and therapy.Science advances · 2025Article
- Increased circulating heat shock protein Hsp70 serum levels as a potential biomarker in bronchial asthma patients.Scientific reports · 2025Article
- Airway sympathectomy attenuates inflammation, transcriptional ratios of Muc5ac and Muc5b, and airway mechanic deficits in mice delivered intranasal IL-13.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Analysis of the effects of perfluorooctane sulfonate on COPD using network toxicology and molecular docking.iScience · 2025Article
- HSP70 is a chaperone for IL-33 activity in chronic airway disease.JCI insight · 2025Article
- Perihematomal Neurovascular Protection: Blocking HSP90 Reduces Blood Infiltration Associated with Inflammatory Effects Following Intracerebral Hemorrhage in Rates.Translational stroke research · 2025Article
- Article
- The extracellular matrix protein periostin is required for wound repair in primary human airway epithelia.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Article
- Club cell-derived brain-derived neurotrophic factor regulates murine airway mechanics and mucin production in response to IL-13 in a sex-dependent manner.Frontiers in physiology · 2025Article
- The role of heat shock protein 90 in idiopathic pulmonary fibrosis: state of the art.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Novel insights into the study of goblet cell hypersecretion in allergic rhinitis.Frontiers in immunology · 2025Review
- Inhibition of Hsp90 K284 Acetylation Aalleviates Cardiac Injury After Ischemia-Reperfusion Injury.Journal of cardiovascular translational research · 2024Article
- IL-13 induces loss of CFTR in ionocytes and reduces airway epithelial fluid absorption.The Journal of clinical investigation · 2024Article
- Interleukin 13-Induced Inflammation Increases DPP4 Abundance but Does Not Enhance Middle East Respiratory Syndrome Coronavirus Replication in Airway Epithelia.The Journal of infectious diseases · 2024Article
- Reduced miR-513a-5p expression in COPD may regulate airway mucous cell hyperplasia through TFR1-dependent signaling.The Kaohsiung journal of medical sciences · 2024Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Goblet cell metaplasia, a disabling hallmark of chronic lung disease, lacks curative treatments at present. To identify novel therapeutic targets for goblet cell metaplasia, we studied the transcriptional response profile of IL-13-exposed primary human airway epithelia in vitro and asthmatic airway epithelia in vivo. A perturbation-response profile connectivity approach identified geldanamycin, an inhibitor of heat shock protein 90 (HSP90) as a candidate therapeutic target. Our experiments confirmed that geldanamycin and other HSP90 inhibitors prevented IL-13-induced goblet cell metaplasia in vitro and in vivo. Geldanamycin also reverted established goblet cell metaplasia. Geldanamycin did not induce goblet cell death, nor did it solely block mucin synthesis or IL-13 receptor-proximal signaling. Geldanamycin affected the transcriptome of airway cells when exposed to IL-13, but not when exposed to vehicle. We hypothesized that the mechanism of action probably involves TGF-β, ERBB, or EHF, which would predict that geldanamycin would also revert IL-17-induced goblet cell metaplasia, a prediction confirmed by our experiments. Our findings suggest that persistent airway goblet cell metaplasia requires HSP90 activity and that HSP90 inhibitors will revert goblet cell metaplasia, despite active upstream inflammatory signaling. Moreover, HSP90 inhibitors may be a therapeutic option for airway diseases with goblet cell metaplasia of unknown mechanism.
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Registered trials
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