CTNNAL1 deficiency suppresses CFTR expression in HDM-induced asthma mouse model through ROCK1-CAL signaling pathway  

作　　者：Di Wu Jiahui Zhu Fang Yang Riwang Li Lexin Liu Dahai Liu Chi Liu Xiangping Qu Huijun Liu Ming Ji Xiaoqun Qin Lan Hua Yang Xiang 

机构地区：[1]School of Medicine,Foshan University,Foshan 528000,China [2]Department of Physiology,School of Basic Medical Science,Central South University,Changsha 410008,China [3]the Second Xiangya Hospital of Central South University,Changsha 410011,China

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第10期1618-1629,共12页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the National Natural Science Foundation of China(Nos.82270413 and 81870307);the Natural Science Foundation of Guangdong Province of China(No.2022A1515011368);the Key Projects of Department of Education of Guangdong Province of China(Nos.2022ZDZX2057 and 2022ZXKC474);the Guangdong Basic and Applied Basic Research Foundation(Nos.2022A11515111169 and 2022A1515110595).

摘　　要：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–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.

关 键 词：ASTHMA CTNNAL1 CFTR ROCK1 CAL 

分 类 号：R562.25[医药卫生—呼吸系统]