CTNNAL1 deficiency suppresses CFTR expression in HDM-induced asthma mouse model through ROCK1-CAL signaling pathway
The downregulation of adhesion molecule catenin alpha-like 1 (CTNNAL1) in airway epithelial cells of asthma patients and house dust mite (HDM)-induced asthma animal models was illustrated in our previous study. It is assumed to contribute t...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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China Science Publishing & Media Ltd.
2023-09-01
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| Series: | Acta Biochimica et Biophysica Sinica |
| Subjects: | |
| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2023152 |
| _version_ | 1797635908922507264 |
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| author | Wu Di Zhu Jiahui Yang Fang Li Riwang Liu Lexin Liu Dahai Liu Chi Qu Xiangping Liu Huijun Ji Ming Qin Xiaoqun Hua Lan Xiang Yang |
| author_facet | Wu Di Zhu Jiahui Yang Fang Li Riwang Liu Lexin Liu Dahai Liu Chi Qu Xiangping Liu Huijun Ji Ming Qin Xiaoqun Hua Lan Xiang Yang |
| author_sort | Wu Di |
| collection | DOAJ |
| description | The downregulation of adhesion molecule catenin alpha-like 1 (CTNNAL1) in airway epithelial cells of asthma patients and house dust mite (HDM)-induced asthma animal models was illustrated in our previous study. It is assumed to contribute to airway inflammation and mucus hypersecretion. In this work, we further explore the underlying mechanism of CTNNAL1 in asthma. CTNNAL1-silenced female mice exhibit a decreased level of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated and ATP-gated Cl<sup>–</sup> channel that correlates with mucus hypersecretion. Our previous study demonstrated that ROCK1 expression decreases but ROCK2 expression increases in the lungs of a CTNNAL1-silenced mouse model. Inhibition of ROCK1 leads to a reduction in CFTR expression in CTNNAL1-overexpressing and CTNNAL1-silenced human bronchial epithelial (HBE) cells. It has been reported that ROCK1 is a downstream target of RhoA and that activation of RhoA increases CFTR expression after CTNNAL1 deficiency in vitro and in vivo. The above results indicate that CTNNAL1 regulates CFTR expression through the ROCK1 pathway. In addition, the expression of CFTR-associated ligand (CAL) is increased after CTNNAL1 silencing, and immunoprecipitation results confirm the interaction between ROCK1 and CAL. Inhibition of CAL does not influence ROCK1 expression but increases CFTR expression in CTNNAL1-silenced HBE cells. These data suggest that CTNNAL1 deficiency decreases CFTR expression in the HDM-induced asthma mouse model through the ROCK1-CAL signaling pathway. |
| first_indexed | 2024-03-11T12:27:37Z |
| format | Article |
| id | doaj.art-8856f65fa8184514a8acc5375d92f022 |
| institution | Directory Open Access Journal |
| issn | 1672-9145 |
| language | English |
| last_indexed | 2024-03-11T12:27:37Z |
| publishDate | 2023-09-01 |
| publisher | China Science Publishing & Media Ltd. |
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| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj.art-8856f65fa8184514a8acc5375d92f0222023-11-06T08:28:22ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452023-09-01551618162910.3724/abbs.202315220d259ccCTNNAL1 deficiency suppresses CFTR expression in HDM-induced asthma mouse model through ROCK1-CAL signaling pathwayWu Di0Zhu Jiahui1Yang Fang2Li Riwang3Liu Lexin4Liu Dahai5Liu Chi6Qu Xiangping7Liu Huijun8Ji Ming9Qin Xiaoqun10Hua Lan11Xiang Yang12["School of Medicine, Foshan University, Foshan 528000, China","Department of Physiology, School of Basic Medical Science, Central South University, Changsha 410008, China"]["Department of Physiology, School of Basic Medical Science, Central South University, Changsha 410008, China"]["School of Medicine, Foshan University, Foshan 528000, China"]["School of Medicine, Foshan University, Foshan 528000, China"]["Department of Physiology, School of Basic Medical Science, Central South University, Changsha 410008, China"]["School of Medicine, Foshan University, Foshan 528000, China"]["Department of Physiology, School of Basic Medical Science, Central South University, Changsha 410008, China"]["Department of Physiology, School of Basic Medical Science, Central South University, Changsha 410008, China"]["Department of Physiology, School of Basic Medical Science, Central South University, Changsha 410008, China"]["Department of Physiology, School of Basic Medical Science, Central South University, Changsha 410008, China"]["Department of Physiology, School of Basic Medical Science, Central South University, Changsha 410008, China"]["the Second Xiangya Hospital of Central South University, Changsha 410011, China"]["Department of Physiology, School of Basic Medical Science, Central South University, Changsha 410008, China"]The downregulation of adhesion molecule catenin alpha-like 1 (CTNNAL1) in airway epithelial cells of asthma patients and house dust mite (HDM)-induced asthma animal models was illustrated in our previous study. It is assumed to contribute to airway inflammation and mucus hypersecretion. In this work, we further explore the underlying mechanism of CTNNAL1 in asthma. CTNNAL1-silenced female mice exhibit a decreased level of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated and ATP-gated Cl<sup>–</sup> channel that correlates with mucus hypersecretion. Our previous study demonstrated that ROCK1 expression decreases but ROCK2 expression increases in the lungs of a CTNNAL1-silenced mouse model. Inhibition of ROCK1 leads to a reduction in CFTR expression in CTNNAL1-overexpressing and CTNNAL1-silenced human bronchial epithelial (HBE) cells. It has been reported that ROCK1 is a downstream target of RhoA and that activation of RhoA increases CFTR expression after CTNNAL1 deficiency in vitro and in vivo. The above results indicate that CTNNAL1 regulates CFTR expression through the ROCK1 pathway. In addition, the expression of CFTR-associated ligand (CAL) is increased after CTNNAL1 silencing, and immunoprecipitation results confirm the interaction between ROCK1 and CAL. Inhibition of CAL does not influence ROCK1 expression but increases CFTR expression in CTNNAL1-silenced HBE cells. These data suggest that CTNNAL1 deficiency decreases CFTR expression in the HDM-induced asthma mouse model through the ROCK1-CAL signaling pathway.https://www.sciengine.com/doi/10.3724/abbs.2023152asthmaCTNNAL1CFTRROCK1CAL |
| spellingShingle | Wu Di Zhu Jiahui Yang Fang Li Riwang Liu Lexin Liu Dahai Liu Chi Qu Xiangping Liu Huijun Ji Ming Qin Xiaoqun Hua Lan Xiang Yang CTNNAL1 deficiency suppresses CFTR expression in HDM-induced asthma mouse model through ROCK1-CAL signaling pathway Acta Biochimica et Biophysica Sinica asthma CTNNAL1 CFTR ROCK1 CAL |
| title | CTNNAL1 deficiency suppresses CFTR expression in HDM-induced asthma mouse model through ROCK1-CAL signaling pathway |
| title_full | CTNNAL1 deficiency suppresses CFTR expression in HDM-induced asthma mouse model through ROCK1-CAL signaling pathway |
| title_fullStr | CTNNAL1 deficiency suppresses CFTR expression in HDM-induced asthma mouse model through ROCK1-CAL signaling pathway |
| title_full_unstemmed | CTNNAL1 deficiency suppresses CFTR expression in HDM-induced asthma mouse model through ROCK1-CAL signaling pathway |
| title_short | CTNNAL1 deficiency suppresses CFTR expression in HDM-induced asthma mouse model through ROCK1-CAL signaling pathway |
| title_sort | ctnnal1 deficiency suppresses cftr expression in hdm induced asthma mouse model through rock1 cal signaling pathway |
| topic | asthma CTNNAL1 CFTR ROCK1 CAL |
| url | https://www.sciengine.com/doi/10.3724/abbs.2023152 |
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