Lyn kinase represses mucus hypersecretion by regulating IL-13-induced endoplasmic reticulum stress in asthma
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...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-02-01
|
| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396416305898 |
| _version_ | 1818566288349331456 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Xing Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T01:51:47Z |
| format | Article |
| id | doaj.art-1f21baedfed946cf9db941763aa89711 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-14T01:51:47Z |
| publishDate | 2017-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-1f21baedfed946cf9db941763aa897112022-12-21T23:21:21ZengElsevierEBioMedicine2352-39642017-02-0115C13714910.1016/j.ebiom.2016.12.010Lyn kinase represses mucus hypersecretion by regulating IL-13-induced endoplasmic reticulum stress in asthmaXing Wang0Xiaoqiong Yang1Yin Li2Xiaoyun Wang3Yun Zhang4Xi Dai5Bin Niu6Juan Wu7Xiefang Yuan8Anjie Xiong9Zhigang Liu10Nanshan Zhong11Min Wu12Guoping Li13Inflammation & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, ChinaInflammation & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, ChinaThe First Clinic College, Chongqing Medical University, Chongqing 401331, ChinaInflammation & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, ChinaState 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, ChinaState 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, ChinaInflammation & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, ChinaFirst Department of Respiratory Disease, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, ChinaInflammation & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, ChinaInflammation & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, ChinaInflammation & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, ChinaState Key Laboratories of Respiratory Disease, Ghuangzhou Medical University, Guangdong 510120, ChinaDepartment of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, 1301 N Columbia Rd, Grand Forks, ND 58203-9037, United StatesInflammation & Allergic Diseases Research Unit, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, ChinaIn 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.http://www.sciencedirect.com/science/article/pii/S2352396416305898Mucus secretionLyn kinaseEndoplasmic reticulum stressMUC5ACAsthma |
| spellingShingle | 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 Lyn kinase represses mucus hypersecretion by regulating IL-13-induced endoplasmic reticulum stress in asthma EBioMedicine Mucus secretion Lyn kinase Endoplasmic reticulum stress MUC5AC Asthma |
| title | Lyn kinase represses mucus hypersecretion by regulating IL-13-induced endoplasmic reticulum stress in asthma |
| title_full | Lyn kinase represses mucus hypersecretion by regulating IL-13-induced endoplasmic reticulum stress in asthma |
| title_fullStr | Lyn kinase represses mucus hypersecretion by regulating IL-13-induced endoplasmic reticulum stress in asthma |
| title_full_unstemmed | Lyn kinase represses mucus hypersecretion by regulating IL-13-induced endoplasmic reticulum stress in asthma |
| title_short | Lyn kinase represses mucus hypersecretion by regulating IL-13-induced endoplasmic reticulum stress in asthma |
| title_sort | lyn kinase represses mucus hypersecretion by regulating il 13 induced endoplasmic reticulum stress in asthma |
| topic | Mucus secretion Lyn kinase Endoplasmic reticulum stress MUC5AC Asthma |
| url | http://www.sciencedirect.com/science/article/pii/S2352396416305898 |
| work_keys_str_mv | AT xingwang lynkinaserepressesmucushypersecretionbyregulatingil13inducedendoplasmicreticulumstressinasthma AT xiaoqiongyang lynkinaserepressesmucushypersecretionbyregulatingil13inducedendoplasmicreticulumstressinasthma AT yinli lynkinaserepressesmucushypersecretionbyregulatingil13inducedendoplasmicreticulumstressinasthma AT xiaoyunwang lynkinaserepressesmucushypersecretionbyregulatingil13inducedendoplasmicreticulumstressinasthma AT yunzhang lynkinaserepressesmucushypersecretionbyregulatingil13inducedendoplasmicreticulumstressinasthma AT xidai lynkinaserepressesmucushypersecretionbyregulatingil13inducedendoplasmicreticulumstressinasthma AT binniu lynkinaserepressesmucushypersecretionbyregulatingil13inducedendoplasmicreticulumstressinasthma AT juanwu lynkinaserepressesmucushypersecretionbyregulatingil13inducedendoplasmicreticulumstressinasthma AT xiefangyuan lynkinaserepressesmucushypersecretionbyregulatingil13inducedendoplasmicreticulumstressinasthma AT anjiexiong lynkinaserepressesmucushypersecretionbyregulatingil13inducedendoplasmicreticulumstressinasthma AT zhigangliu lynkinaserepressesmucushypersecretionbyregulatingil13inducedendoplasmicreticulumstressinasthma AT nanshanzhong lynkinaserepressesmucushypersecretionbyregulatingil13inducedendoplasmicreticulumstressinasthma AT minwu lynkinaserepressesmucushypersecretionbyregulatingil13inducedendoplasmicreticulumstressinasthma AT guopingli lynkinaserepressesmucushypersecretionbyregulatingil13inducedendoplasmicreticulumstressinasthma |