AJP - Lung Watch the video to learn how APS reaches out to developing nations.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Lung Cell Mol Physiol 296: L684-L692, 2009. First published February 6, 2009; doi:10.1152/ajplung.90396.2008
1040-0605/09 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
296/4/L684    most recent
90396.2008v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Web of Science (1)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Song, K. S.
Right arrow Articles by Yoon, J.-H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Song, K. S.
Right arrow Articles by Yoon, J.-H.

TRANSLATIONAL PHYSIOLOGY

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

Kyoung Seob Song,1 Yeon Ho Choi,3,4 Jong-Mu Kim,3,4 Hyunjae Lee,3,4 Tae-Jin Lee,5 and Joo-Heon Yoon1,2,3,4

1The Airway Mucus Institute, 2Department of Otorhinolaryngology, 3Brain Korea 21 for Medical Sciences, and 4Research Center for Human Natural Defense System, Yonsei University College of Medicine, Seoul; and 5Department of Anatomy, College of Medicine, Yeungnam University, Taegu, Korea

Submitted 24 July 2008 ; accepted in final form 31 January 2009

The mechanism by which E-prostanoid (EP) receptor is critically involved in PGE2-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 PGE2-induced MUC5AC overproduction. In the present study, we found that PGE2 induced MUC5AC gene expression in a dose-dependent manner (EC50: 73.31 ± 3.13 nM) and that the EP2/4-specific agonist, misoprostol, increased MUC5AC mRNA level, whereas the EP1/3-specific agonist, sulprostone, had no effect. Interestingly, the cAMP concentration (685.1 ± 14.9 pM) of the EC50 value of EP4-mediated cAMP production was much higher than that of EP2 (462.33 ± 23.79 pM), suggesting that EP4 has higher sensitivity to PGE2 compared with EP2. Moreover, PGE2-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 PGE2 can induce MUC5AC overproduction via the EP4 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.

inflammation; mucin 5AC; EP4; regulator of G protein signaling-4


Address for reprint requests and other correspondence: J.-H. Yoon, Dept. of Otorhinolaryngology, Yonsei Univ. College of Medicine, 134 Shinchon-Dong, Seodaemun-gu, Seoul 120-752, Korea (e-mail: jhyoon{at}yuhs.ac)






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2009 by the American Physiological Society.