期刊
EBIOMEDICINE
卷 33, 期 -, 页码 242-252出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ebiom.2018.06.032
关键词
TGF-beta/3; MUC5AC; Autophagy; Smad2/3
资金
- National Natural Science Foundation of China [81600024]
- Health and Family Planning Commission of Sichuan Province [16PJ543]
Mucus secretion accumulation in the airways may act as a contributing factor for the development of airflow limitation in severe fetal asthma patients. Accumulated evidences showed that transforming growth factor beta (TGF-beta 3) plays a regulatory role in airway remodeling including mucus hyper-secretion in asthma. However. the detailed molecular mechanisms of TGI-beta 3 induced MUC5AC hyper-expression in airway epithelium remains unclear. Here, we demonstrated the pivotal roles of autophagy in regulation of MUC5AC hyper-production induced by TGF-beta 3 in airway epithelium. Our experimental data showed that inhibiting autophagy pathway in repeated ovalbumin (OVA) exposed mice exhibited decreased airway hyper-response and airway inflammation, diminishing the expression of Muc5ac and TGF-beta 3. Furthermore, our studies demonstrated that autophagy was induced upon exposure to TGF-beta 3 and then mediated MUC5AC hyper-expression by activating the activator protein-1 (AP-1) in human bronchial epithelial cells. Finally, Smad2/3 pathway was involved in TGF-beta 3-induced MUC5AC hyper-expressions by promoting autophagy. These data indicated that autophagy was required for TGF beta 3 induced airway mucous hyper-production, and that inhibition of autophagy exerted therapeutic benefits for TGF-beta 3 induced airway mucus secretion. (C) 2018 The Authors. Published by Elsevier B.V.
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