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The role of secreted Hsp90α in HDM-induced asthmatic airway epithelial barrier dysfunction

BACKGROUND: The dysfunction of airway epithelial barrier is closely related to the pathogenesis of asthma. Secreted Hsp90α participates in inflammation and Hsp90 inhibitor protects endothelial dysfunction. In the current study, we aimed to explore the role of secreted Hsp90α in asthmatic airway epit...

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Autores principales: Ye, Cuiping, Huang, Chaowen, Zou, Mengchen, Hu, Yahui, Luo, Lishan, Wei, Yilan, Wan, Xuan, Zhao, Haijin, Li, Wei, Cai, Shaoxi, Dong, Hangming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868813/
https://www.ncbi.nlm.nih.gov/pubmed/31747880
http://dx.doi.org/10.1186/s12890-019-0938-z
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author Ye, Cuiping
Huang, Chaowen
Zou, Mengchen
Hu, Yahui
Luo, Lishan
Wei, Yilan
Wan, Xuan
Zhao, Haijin
Li, Wei
Cai, Shaoxi
Dong, Hangming
author_facet Ye, Cuiping
Huang, Chaowen
Zou, Mengchen
Hu, Yahui
Luo, Lishan
Wei, Yilan
Wan, Xuan
Zhao, Haijin
Li, Wei
Cai, Shaoxi
Dong, Hangming
author_sort Ye, Cuiping
collection PubMed
description BACKGROUND: The dysfunction of airway epithelial barrier is closely related to the pathogenesis of asthma. Secreted Hsp90α participates in inflammation and Hsp90 inhibitor protects endothelial dysfunction. In the current study, we aimed to explore the role of secreted Hsp90α in asthmatic airway epithelial barrier function. METHODS: Male BALB/c mice were sensitized and challenged with HDM to generate asthma model. The 16HBE and Hsp90α-knockdown cells were cultured and treated according to the experiment requirements. Transepithelial Electric Resistance (TEER) and permeability of epithelial layer in vitro, distribution and expression of junction proteins both in vivo and in vitro were used to evaluate the epithelial barrier function. Western Blot was used to evaluate the expression of junction proteins and phosphorylated AKT in cells and lung tissues while ELISA were used to evaluate the Hsp90α expression and cytokines release in the lung homogenate. RESULTS: HDM resulted in a dysfunction of airway epithelial barrier both in vivo and in vitro, paralleled with the increased expression and release of Hsp90α. All of which were rescued in Hsp90α-knockdown cells or co-administration of 1G6-D7. Furthermore, either 1G6-D7 or PI3K inhibitor LY294002 suppressed the significant phosphorylation of AKT, which caused by secreted and recombinant Hsp90α, resulting in the restoration of epithelial barrier function. CONCLUSIONS: Secreted Hsp90α medicates HDM-induced asthmatic airway epithelial barrier dysfunction via PI3K/AKT pathway, indicating that anti-secreted Hsp90α therapy might be a potential treatment to asthma in future.
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spelling pubmed-68688132019-12-12 The role of secreted Hsp90α in HDM-induced asthmatic airway epithelial barrier dysfunction Ye, Cuiping Huang, Chaowen Zou, Mengchen Hu, Yahui Luo, Lishan Wei, Yilan Wan, Xuan Zhao, Haijin Li, Wei Cai, Shaoxi Dong, Hangming BMC Pulm Med Research Article BACKGROUND: The dysfunction of airway epithelial barrier is closely related to the pathogenesis of asthma. Secreted Hsp90α participates in inflammation and Hsp90 inhibitor protects endothelial dysfunction. In the current study, we aimed to explore the role of secreted Hsp90α in asthmatic airway epithelial barrier function. METHODS: Male BALB/c mice were sensitized and challenged with HDM to generate asthma model. The 16HBE and Hsp90α-knockdown cells were cultured and treated according to the experiment requirements. Transepithelial Electric Resistance (TEER) and permeability of epithelial layer in vitro, distribution and expression of junction proteins both in vivo and in vitro were used to evaluate the epithelial barrier function. Western Blot was used to evaluate the expression of junction proteins and phosphorylated AKT in cells and lung tissues while ELISA were used to evaluate the Hsp90α expression and cytokines release in the lung homogenate. RESULTS: HDM resulted in a dysfunction of airway epithelial barrier both in vivo and in vitro, paralleled with the increased expression and release of Hsp90α. All of which were rescued in Hsp90α-knockdown cells or co-administration of 1G6-D7. Furthermore, either 1G6-D7 or PI3K inhibitor LY294002 suppressed the significant phosphorylation of AKT, which caused by secreted and recombinant Hsp90α, resulting in the restoration of epithelial barrier function. CONCLUSIONS: Secreted Hsp90α medicates HDM-induced asthmatic airway epithelial barrier dysfunction via PI3K/AKT pathway, indicating that anti-secreted Hsp90α therapy might be a potential treatment to asthma in future. BioMed Central 2019-11-20 /pmc/articles/PMC6868813/ /pubmed/31747880 http://dx.doi.org/10.1186/s12890-019-0938-z Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Ye, Cuiping
Huang, Chaowen
Zou, Mengchen
Hu, Yahui
Luo, Lishan
Wei, Yilan
Wan, Xuan
Zhao, Haijin
Li, Wei
Cai, Shaoxi
Dong, Hangming
The role of secreted Hsp90α in HDM-induced asthmatic airway epithelial barrier dysfunction
title The role of secreted Hsp90α in HDM-induced asthmatic airway epithelial barrier dysfunction
title_full The role of secreted Hsp90α in HDM-induced asthmatic airway epithelial barrier dysfunction
title_fullStr The role of secreted Hsp90α in HDM-induced asthmatic airway epithelial barrier dysfunction
title_full_unstemmed The role of secreted Hsp90α in HDM-induced asthmatic airway epithelial barrier dysfunction
title_short The role of secreted Hsp90α in HDM-induced asthmatic airway epithelial barrier dysfunction
title_sort role of secreted hsp90α in hdm-induced asthmatic airway epithelial barrier dysfunction
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868813/
https://www.ncbi.nlm.nih.gov/pubmed/31747880
http://dx.doi.org/10.1186/s12890-019-0938-z
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