Open AccessGLCCI1 reduces collagen deposition and airway hyper‐responsiveness in a mouse asthma model through binding with WD repeat domain 45B
Author(s) -
Xun Qiufen,
Kuang Jiulong,
Yang Qing,
Wang Wei,
Zhu Guofeng
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16658
Subject(s) - autophagy , ovalbumin , glucocorticoid , asthma , in vivo , immunology , in vitro , interleukin 13 , autophagosome , microbiology and biotechnology , chemistry , biology , medicine , interleukin 4 , immune system , biochemistry , apoptosis
Asthma is a serious public health problem worldwide, without effective therapeutic methods. Our previous study indicated that glucocorticoid‐induced transcript 1 gene (GLCCI1) knockout reduces the sensitivity to glucocorticoid in asthmatic mouse. Here, we explored the role and action mechanism of GLCCI1 in asthma development. In ovalbumin‐sensitized mice, airway resistance and tissue damage increased, the production of inflammatory cytokines were up‐regulated, GLCCI1 expression was reduced and autophagy was activated. Increasing of GLCCI1 inhibited human and mouse airway epithelial cell (AEC) autophagy, while decreasing of GLCCI1 promoted autophagy. Furthermore, we found that GLCCI1 bound with WD repeat domain 45B (WDR45B) and inhibited its expression. Increasing of WDR45B partly reversed the inhibition of GLCCI1 to autophagy‐related proteins expression and autophagosome formation in vitro. Increasing of WDR45B in vivo reversed the improvement of GLCCI1 on airway remodelling in asthma and the inhibition to autophagy level in lung tissues. Overall, our data showed that GLCCI1 improved airway remodelling in ovalbumin‐sensitized mice through inhibiting autophagy via combination with WDR45B and inhibiting its expression. Our results proved a new idea for asthma treatment.