ArticleRespiratory research2017
Extracellular heat shock protein 90α mediates HDM-induced bronchial epithelial barrier dysfunction by activating RhoA/MLC signaling.
Article in Respiratory research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- Targeting eHsp90α/GRP78 signaling-mediated endothelial barrier dysfunction in diabetic atherosclerosis: evidence from clinical and experimental studies.Molecular and cellular biochemistry · 2026Article
- Increased circulating heat shock protein Hsp70 serum levels as a potential biomarker in bronchial asthma patients.Scientific reports · 2025Article
- Advances in the structures, mechanisms and targeting of molecular chaperones.Signal transduction and targeted therapy · 2025Review
- Low-density lipoprotein receptor-related protein 6 ameliorates cardiac hypertrophy by regulating CTSD/HSP90α signaling during pressure overload.Acta pharmacologica Sinica · 2025Article
- Precision medicine for asthma treatment: Unlocking the potential of the epigenome and microbiome.The Journal of allergy and clinical immunology · 2025Review
- Integrating multi-omics, network pharmacology, and experimental validation to unveil the molecular mechanisms ofFrontiers in pharmacology · 2025Article
- HMOS 2'FL and 3FL prevent house dust mite induced proinflammatory cytokine releaseFrontiers in nutrition · 2025Article
- REV-ERBα agonist SR10067 attenuates Th2 cytokine-mediated barrier dysfunction in human bronchial epithelial cells.Clinical science (London, England : 1979) · 2024Article
- Protective role of the HSP90 inhibitor, STA-9090, in lungs of SARS-CoV-2-infected Syrian golden hamsters.BMJ open respiratory research · 2024Article
- A Differential Protein Study on Bronchoalveolar Lavage Fluid at Different Stages of Silicosis.Combinatorial chemistry & high throughput screening · 2024Article
- GW4869 Can Inhibit Epithelial-Mesenchymal Transition and Extracellular HSP90α in Gefitinib-Sensitive NSCLC Cells.OncoTargets and therapy · 2023Article
- Epithelial coxsackievirus adenovirus receptor promotes house dust mite-induced lung inflammation.Nature communications · 2022Article
- Streptococcal autolysin promotes dysfunction of swine tracheal epithelium by interacting with vimentin.PLoS pathogens · 2022Article
- [HSP90α exacerbates house dust mite-induced asthmatic airway inflammation by upregulating endoplasmic reticulum stress in bronchial epithelial cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- Review
- Avasimibe Alleviates Disruption of the Airway Epithelial Barrier by Suppressing the Wnt/β-Catenin Signaling Pathway.Frontiers in pharmacology · 2022Article
- RhoA/Rho-kinases in asthma: from pathogenesis to therapeutic targets.Clinical & translational immunology · 2020Review
- Immunologic and Non-Immunologic Mechanisms Leading to Airway Remodeling in Asthma.International journal of molecular sciences · 2020Review
- The role of secreted Hsp90α in HDM-induced asthmatic airway epithelial barrier dysfunction.BMC pulmonary medicine · 2019Article
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe disruption and hyperpermeability of bronchial epithelial barrier are closely related to the pathogenesis of asthma. House dust mite (HDM), one of the most important allergens, could increase the airway epithelial permeability. Heat shock protein (Hsp) 90α is also implicated in the lung endothelial barrier dysfunction by disrupting RhoA signaling. However, the effect of extracellular Hsp90α (eHsp90α) on the bronchial epithelial barrier disruption induced by HDM has never been reported.
methodsTo investigate the involvement of eHsp90α in the bronchial epithelial barrier disruption induced by HDM, normal human bronchial epithelial cell line 16HBE14o- (16HBE) cells were treated by HDM, human recombinant (hr) Hsp90α and hrHsp90β respectively and pretreated by1G6-D7, a specific anti-secreted Hsp90α monoclonal antibody (mAb). Hsp90α-silencing cells were also constructed. To further evaluate the role of RhoA signaling in this process, cells were pretreated by inhibitors of Rho kinase, GSK429286A and Y27632 2HCl. Transepithelial electrical resistance (TEER) and FITC-dextran flux (FITC-DX) were examined as the epithelial barrier function. Expression and localization of adherens junctional proteins E-cadherin and β-catenin were evaluated by western blotting and immunofluorescence respectively. The level of eHsp90α was investigated by concentration and purification of condition media. RhoA activity was determined by using a Rho G-LISA® RhoA activation assay kit
resultsThe epithelial barrier disruption and the loss of adherens junctional proteins E-cadherin and β-catenin in cytomembrane were observed in HDM-treated 16HBE cells, paralleled with the increase of eHsp90α secretion. All of which were rescued in Hsp90α-silencing cells or by pretreating 16HBE cells with 1G6-D7. Also, 1G6-D7 suppressed RhoA activity and MLC phosphorylation induced by HDM. Furthermore, inhibitors of Rho kinase prevented and restored the airway barrier disruption. Consistently, it was hrHsp90α instead of hrHsp90β that promoted barrier dysfunction and activated RhoA/MLC signaling in 16HBE cells.
conclusionsThe eHsp90α mediates HDM-induced human bronchial epithelial barrier dysfunction by activating RhoA/MLC signaling, suggesting that eHsp90α is a potential therapeutic target for treatment of asthma.
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