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Suppression of prostaglandin E2-induced MUC5AC overproduction by RGS4 in the airway.

Authors
 Kyoung Seob Song  ;  Yeon Ho Choi  ;  Jong-Mu Kim  ;  Hyunjae Lee  ;  Tae-Jin Lee  ;  Joo-Heon Yoon 
Citation
 AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, Vol.296(4) : 684-692, 2009 
Journal Title
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
ISSN
 1040-0605 
Issue Date
2009
MeSH
Animals ; Cell Line ; Dinoprostone/pharmacology* ; GTP-Binding Protein alpha Subunits, Gs/metabolism ; Gene Expression Regulation/drug effects ; Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology ; Humans ; Mice ; Mucin 5AC/genetics ; Mucin 5AC/metabolism* ; RGS Proteins/metabolism* ; Receptors, Prostaglandin E/metabolism ; Receptors, Prostaglandin E, EP4 Subtype ; Trachea/metabolism*
Abstract
The mechanism by which E-prostanoid (EP) receptor is critically involved in PGE(2)-induced mucin 5AC (MUC5AC) gene expression in the airway has been unclear. Furthermore, there have been little reports regarding the negative regulatory mechanism and/or proteins that affect PGE(2)-induced MUC5AC overproduction. In the present study, we found that PGE(2) induced MUC5AC gene expression in a dose-dependent manner (EC(50): 73.31 +/- 3.13 nM) and that the EP(2/4)-specific agonist, misoprostol, increased MUC5AC mRNA level, whereas the EP(1/3)-specific agonist, sulprostone, had no effect. Interestingly, the cAMP concentration (685.1 +/- 14.9 pM) of the EC(50) value of EP(4)-mediated cAMP production was much higher than that of EP(2) (462.33 +/- 23.79 pM), suggesting that EP(4) has higher sensitivity to PGE(2) compared with EP(2). Moreover, PGE(2)-induced Muc5ac overproduction was much increased in regulator of G protein signaling (Rgs) 4 knockout (KO) mice compared with wild-type mice at both transcriptional and translational levels, and it was dramatically suppressed in Rgs4 KO mice that had been infected with lentivirus expressing RGS4 (lenti::RGS4) compared with lentivirus expressing enhanced green fluorescent protein (lenti::eGFP). Finally, we demonstrate that PGE(2) can induce MUC5AC overproduction via the EP(4) receptor and that RGS4 may have suppressive effects in controlling MUC5AC overexpression in the airway. These findings may provide a molecular paradigm for the development of novel drugs for respiratory diseases.
Files in This Item:
T200900655.pdf Download
DOI
10.1152/ajplung.90396.2008
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
6. Others (기타) > Others (기타) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Jong Mu(김종무)
Song, Kyoung Seob(송경섭)
Yoon, Joo Heon(윤주헌)
Lee, Hyun Jae(이현재)
Choi, Yeon Ho(최연호)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/103600
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