Lyn kinase represses mucus hypersecretion by regulating IL-13-induced endoplasmic reticulum stress in asthma
Xing Wang,
Xiaoqiong Yang,
Yin Li,
Xiaoyun Wang,
Yun Zhang,
Xi Dai,
Bin Niu,
Juan Wu,
Xiefang Yuan,
Anjie Xiong,
Zhigang Liu,
Nanshan Zhong,
Min Wu,
Guoping Li
Affiliations
Xing Wang
Inflammation & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China
Xiaoqiong Yang
Inflammation & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China
Yin Li
The First Clinic College, Chongqing Medical University, Chongqing 401331, China
Xiaoyun Wang
Inflammation & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China
Yun Zhang
State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macao, China
Xi Dai
State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macao, China
Bin Niu
Inflammation & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China
Juan Wu
First Department of Respiratory Disease, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China
Xiefang Yuan
Inflammation & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China
Anjie Xiong
Inflammation & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China
Zhigang Liu
Inflammation & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China
Nanshan Zhong
State Key Laboratories of Respiratory Disease, Ghuangzhou Medical University, Guangdong 510120, China
Min Wu
Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, 1301 N Columbia Rd, Grand Forks, ND 58203-9037, United States
Guoping Li
Inflammation & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China
In asthma, mucus hypersecretion is thought to be a prominent pathological feature associated with widespread mucus plugging. However, the current treatments for mucus hypersecretion are often ineffective or temporary. The potential therapeutic targets of mucus hypersecretion in asthma remain unknown. Here, we show that Lyn is a central effector of endoplasmic reticulum stress (ER stress) and mucous hypersecretion in asthma. In Lyn-transgenic mice (Lyn-TG) and wild-type (WT) C57BL/6J mice exposed to ovalbumin (OVA), Lyn overexpression attenuates mucus hypersecretion and ER stress. Interleukin 13 (IL-13) induced MUC5AC expression by enhancing ER stress in vitro. Lyn serves as a negative regulator of IL-13-induced ER stress and MUC5AC expression. We further find that an inhibitor of ER stress, which is likely involved in the PI3K p85α/Akt pathway and NFκB activity, blocked MUC5AC expression in Lyn-knockdown cells. Furthermore, PI3K/Akt signaling is required for IL-13-induced ER stress and MUC5AC expression in airway epithelial cells. The ER stress regulation of MUC5AC expression depends on NFκB in Lyn-knockdown airway epithelial cells. Our studies indicate not only a concept of mucus hypersecretion in asthma that involves Lyn kinase but also an important therapeutic candidate for asthma.