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House dust mite-induced endoplasmic reticulum stress mediates mucus MUC5AC hyper secretion via TBK1-STAT6/NF-κB in asthmatic mice
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  • Yun Zhang,
  • Hongmei Tang,
  • Xiefang Yuan,
  • ning ma,
  • Hang Hu,
  • Xiaoyun Wang,
  • Chunfeng Liu,
  • Guofeng Xu,
  • Yuejiao Li,
  • Songping Wang,
  • Linlin Guo,
  • Jun Deng,
  • Xing Wang
Yun Zhang
The Affiliated Hospital of Southwest Medical University
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Hongmei Tang
The Affiliated Hospital of Southwest Medical University
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Xiefang Yuan
The Affiliated Hospital of Southwest Medical University
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ning ma
The Affiliated Hospital of Southwest Medical University
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Hang Hu
The Affiliated Hospital of Southwest Medical University
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Xiaoyun Wang
The Affiliated Hospital of Southwest Medical University
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Chunfeng Liu
The Affiliated Hospital of Southwest Medical University
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Guofeng Xu
The Affiliated Hospital of Southwest Medical University
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Yuejiao Li
The Affiliated Hospital of Southwest Medical University
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Songping Wang
The Affiliated Hospital of Southwest Medical University
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Linlin Guo
The Ohio State University Wexner Medical Center
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Jun Deng
The Affiliated Hospital of Southwest Medical University
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Xing Wang
The Affiliated Hospital of Southwest Medical University
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Abstract

ABSTRACT Background Exposed to house dust mite (HDM) is known to be associated with allergic asthma. Endoplasmic reticulum (ER) stress is involved in the regulation of mucus hyper secretion. However, the mechanism remains unclear. Our main goal was to investigate the relationship of TBK1 pathway regulates the expression of MUC5AC under the HDM induced ER stress promote allergic asthma. Methods Using HDM induced allergic mice and stimulated over expression of MUC5AC in human airway epithelial cells. We examined the mucus and the expression of ER stress markers both in vivo and in vitro. Additionally, we investigated whether TBK1, NF-κB, STAT6 play an important role in the HDM induced ER stress promote airway mucus hyper secretion. Results Mice exposed to HDM were identified ER stress, hyper secretion of mucus, and activated TBK1-NF-κB/STAT6 signaling pathway in airway epithelial cells of asthmatic mice. Similarly results had also been observed in the human airway epithelial cells after exposed to HDM. Both in vivo and in vitro study not only revealed that an anti-allergy drug, Amlexanox, reduced super response of mucus and weaken TBK1-NF-κB/STAT6 signal of induced asthma. But also indicated HDM induced ER stress result in over production of MUC5AC, which can be decreased by the inhibition of TBK1, NF-κB, STAT6, or even by using ER stress inhibitor 4-PBA, respectively. Conclusions Our results show that TBK1-NF-κB/STAT6 plays a pivotal role in the HDM induced ER stress result in over production of mucus protein MUC5AC in the asthmatic airway.