Lyn kinase represses mucus hypersecretion by regulating IL-13-induced endoplasmic reticulum stress in asthma
| Autor: | Xiaoyun Wang, Min Wu, Zhigang Liu, Xiefang Yuan, Anjie Xiong, Juan Wu, Yin Li, Nanshan Zhong, Xi Dai, Guoping Li, Xing Wang, Yun Zhang, Bin Niu, Xiaoqiong Yang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male lcsh:Medicine Mucin 5AC Mice Phosphatidylinositol 3-Kinases 0302 clinical medicine fluids and secretions hemic and lymphatic diseases lcsh:R5-920 Interleukin-13 biology NF-kappa B hemic and immune systems General Medicine respiratory system Lyn kinase src-Family Kinases 030220 oncology & carcinogenesis Gene Knockdown Techniques Interleukin 13 Mucus secretion Endoplasmic reticulum stress Cytokines Female lcsh:Medicine (General) Research Paper Signal Transduction medicine.medical_specialty Ovalbumin Mice Transgenic Models Biological General Biochemistry Genetics and Molecular Biology 03 medical and health sciences LYN Internal medicine medicine Animals Humans Protein kinase B PI3K/AKT/mTOR pathway Endoplasmic reticulum lcsh:R MUC5AC Mucus Asthma Disease Models Animal 030104 developmental biology Endocrinology Case-Control Studies Cancer research Unfolded protein response biology.protein Proto-Oncogene Proteins c-akt Biomarkers |
| Zdroj: | EBioMedicine, Vol 15, Iss C, Pp 137-149 (2017) EBioMedicine |
| ISSN: | 2352-3964 |
| Popis: | 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. Highlights • ER stress may be critical for the pathogenesis of bronchial asthma, especially the steroid-resistant neutrophilic asthma. • We confirmed that Lyn serves as a negative regulator of ER stress and MUC5AC through PI3K p85α/Akt/NFκB pathway in asthma. • This indicates not only a concept of mucus hypersecretion that involves Lyn but also a therapeutic candidate for asthma. |
| Databáze: | OpenAIRE |
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