Previously, we found that bombesin receptor subtype 3 (BRS-3) significantly increased in an ozone-stressed airway hyperresponsiveness animal model and resulted in induced wound repair and protection from acute lung injury. In the present study, we determined molecular mechanisms of BRS-3 regulation in human BECs (bronchial epithelial cells) in response to ozone stress. Ten oligonucleotide probes corresponding to various regions of the BRS-3 promoter were used in EMSA (electrophoretic mobilityshift assays). Four were found to have an enhanced mobility shift with extracts from ozone-stressed cells. On the basis of the assay of mutated probes binding with extracts and antibody supershift, they were verified as MTF-1 (metal-regulatory-element-binding transcription factor-1), PPARα (peroxisome-proliferator-activated receptor α), AP-2α (activator protein 2α) and HSF-1 (heat-shock factor 1). Next, ChIP (chromatin immunoprecipitation) assay, site-directed mutagenesis technology and antisense oligonucleotide technology were used to observe these transcription factors associated with the BRS-3 promoter. Only AP-2α and PPARα increased ozone-inducible DNA binding on the BRS-3 promoter and BRS-3 expression. The time courses of AP-2α and PPARα activation, followed by BRS-3 expression, were also examined. It was shown that ozone-inducible BRS-3 expression and AP-2α- and PPARα-binding activity correlated over a 48 h period. The translocation of PPARα was observed by immunofluorescence assay, which showed that PPARα nuclear translocation increased after ozone exposure. Our data suggest that AP-2α and PPARα may be especially involved in this ozone-inducible up-regulation mechanism of BRS-3 expression.
Skip Nav Destination
Article navigation
July 2007
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
June 13 2007
PPARα and AP-2α regulate bombesin receptor subtype 3 expression in ozone-stressed bronchial epithelial cells
Yu-rong Tan;
Yu-rong Tan
*Department of Physiology, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan, China
Search for other works by this author on:
Xiao-qun Qin;
Xiao-qun Qin
1
*Department of Physiology, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan, China
1To whom correspondence should be addressed (email xiaoqun1988@xysm.net).
Search for other works by this author on:
Yang Xiang;
Yang Xiang
*Department of Physiology, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan, China
Search for other works by this author on:
Tao Yang;
Tao Yang
*Department of Physiology, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan, China
Search for other works by this author on:
Fei Qu;
Fei Qu
*Department of Physiology, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan, China
Search for other works by this author on:
Yue Wang;
Yue Wang
*Department of Physiology, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan, China
Search for other works by this author on:
Hui-jun Liu;
Hui-jun Liu
*Department of Physiology, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan, China
Search for other works by this author on:
H. Christian Weber
H. Christian Weber
†Section of Gastroenterology, Boston University School of Medicine, Boston, MA 02118, U.S.A.
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
November 24 2006
Revision Received:
March 06 2007
Accepted:
March 13 2007
Accepted Manuscript online:
March 13 2007
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2007 Biochemical Society
2007
Biochem J (2007) 405 (1): 131–137.
Article history
Received:
November 24 2006
Revision Received:
March 06 2007
Accepted:
March 13 2007
Accepted Manuscript online:
March 13 2007
Citation
Yu-rong Tan, Xiao-qun Qin, Yang Xiang, Tao Yang, Fei Qu, Yue Wang, Hui-jun Liu, H. Christian Weber; PPARα and AP-2α regulate bombesin receptor subtype 3 expression in ozone-stressed bronchial epithelial cells. Biochem J 1 July 2007; 405 (1): 131–137. doi: https://doi.org/10.1042/BJ20061754
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.