• Yan-Ping Wu, Yin-Fang Wu, Chao Zhang, Hong-Bin Zhou, Chao Cao, Miao Li, Chen Zhu, Song-Min Ying, Zhi-Hua Chen, Hua-Hao Shen, and Wen Li.
• Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
• Am. J. Pathol. 2017 Feb 1; 187 (2): 280-291.

AbstractMucus hypersecretion is an important pathologic feature of chronic obstructive pulmonary disease. Activating transcription factor 3 (ATF3) is an adaptive-response gene that participates in various cellular processes. However, little is known about its role in cigarette smoke (CS)-induced mucus hyperproduction. This study aimed to investigate the role and molecular mechanisms of ATF3 in CS-induced Mucin 5AC (MUC5AC) expression. ATF3 was elevated in lung tissues of mice exposed to CS for 12 weeks. Treatment with CS extract significantly induced ATF3 expression and MUC5AC production in human bronchial epithelial cells, NCI-H292, and mouse tracheal epithelial cells. Interference of ATF3 significantly attenuated CS-induced MUC5AC expression in NCI-H292 and human bronchial epithelial cells. Mouse tracheal epithelial cells isolated from Atf3-/- mice also exhibited less MUC5AC production in response to CS extract treatment. In vivo, the Atf3-/- mice also displayed a significantly reduced mucus production relative to wild-type controls in response to chronic CS exposure. Furthermore, a chromatin immunoprecipitation assay revealed increased ATF3 binding to the MUC5AC promoter after CS treatment, and this transcriptional binding was significantly inhibited by knockdown of JUN, a subunit of activator protein-1. These results demonstrate that ATF3 may be involved in activator protein-1 signaling and transcriptional promotion of CS-induced MUC5AC expression in airway epithelial cells.Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

25 keywords...

hide…