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Extracellular heat shock protein 90α mediates HDM-induced bronchial epithelial barrier dysfunction by activating RhoA/MLC signaling

Overview of attention for article published in Respiratory Research, May 2017
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Title
Extracellular heat shock protein 90α mediates HDM-induced bronchial epithelial barrier dysfunction by activating RhoA/MLC signaling
Published in
Respiratory Research, May 2017
DOI 10.1186/s12931-017-0593-y
Pubmed ID
Authors

Hang-ming Dong, Yan-qing Le, Yan-hong Wang, Hai-jin Zhao, Chao-wen Huang, Ya-hui Hu, Li-shan Luo, Xuan Wan, Yi-lan Wei, Zi-qiang Chu, Wei Li, Shao-xi Cai

Abstract

The 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. To 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(TM) biochem kit, and the phosphorylation of myosin light chain (MLC), the downstream signal molecule of RhoA, was assessed by western blotting. The 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. The 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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The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 31 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 19%
Student > Doctoral Student 4 13%
Student > Master 3 10%
Student > Bachelor 2 6%
Professor > Associate Professor 2 6%
Other 4 13%
Unknown 10 32%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 5 16%
Medicine and Dentistry 4 13%
Agricultural and Biological Sciences 3 10%
Immunology and Microbiology 2 6%
Engineering 2 6%
Other 4 13%
Unknown 11 35%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 06 June 2017.
All research outputs
#17,289,387
of 25,382,440 outputs
Outputs from Respiratory Research
#2,216
of 3,062 outputs
Outputs of similar age
#210,442
of 329,744 outputs
Outputs of similar age from Respiratory Research
#76
of 80 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,062 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.9. This one is in the 18th percentile – i.e., 18% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 329,744 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 27th percentile – i.e., 27% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 80 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.