TGF-β3 Promotes MUC5AC Hyper-Expression by Modulating Autophagy Pathway in Airway Epithelium

EBioMedicine
Yun ZhangXing Wang

Abstract

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-β) plays a regulatory role in airway remodeling including mucus hyper-secretion in asthma. However, the detailed molecular mechanisms of TGF-β3 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-β3 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-β3. Furthermore, our studies demonstrated that autophagy was induced upon exposure to TGF-β3 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-β3-induced MUC5AC hyper-expressions by promoting autophagy. These data indicated that autophagy was required for TGF-β3 induced airway mucous hyper-production, and that inhibition of autophagy exert...Continue Reading

Citations

Aug 14, 2018·Cellular and Molecular Life Sciences : CMLS·Marta MichalikZbigniew Madeja
Mar 19, 2020·International Journal of Molecular Medicine·Yun ZhangXing Wang
Oct 29, 2020·Clinical and Translational Allergy·Chunrong HuangGuochao Shi
Jun 5, 2021·Frontiers in Immunology·Ekaterina O GubernatorovaMarina S Drutskaya

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Methods Mentioned

BETA
bronchoalveolar lavage
ELISA
bronchoalveolar
lavage
Transfection
PCR
transfect
biopsy

Software Mentioned

Leica Application Suite
SPSS

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