help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on February 2, 2006, doi:10.1165/rcmb.2005-0306OC

Am. J. Respir. Cell Mol. Biol., Volume 34, Number 6, June 2006, 695-703

A more recent version of this article appeared on June 1, 2006
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2005-0306OCv1
34/6/695    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Day, R. M
Right arrow Articles by Suzuki, Y. J
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Day, R. M
Right arrow Articles by Suzuki, Y. J

Submitted on August 8, 2005
Revised on February 1, 2006

Retinoic Acid Inhibits Airway Smooth Muscle Cell Migration

Regina M Day1, Young H Lee1, Ah-Mee Park2, and Yuichiro J Suzuki2*

1 Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA, 2 Department of Pharmacology, Georgetown University Medical Center, Washington, DC, USA

* To whom correspondence should be addressed. E-mail: ys82{at}georgetown.edu.

Airway remodeling in chronic asthma is characterized by increased smooth muscle mass that is associated with the reduction of the bronchial lumen as well as airway hyperresponsiveness. The development of agents that inhibit smooth muscle growth is therefore of interest for therapy to prevent asthma-associated airway remodeling. All-trans retinoic acid (ATRA) suppresses growth of vascular smooth muscle cells (SMC) from the systemic and pulmonary circulation. The present study investigated the effects of ATRA on human bronchial (airway) SMC. Human bronchial SMC were found to express mRNAs for retinoic acid receptor (RAR)-{alpha}, -{beta}, -{gamma}, and retinoid X receptor (RXR)-{alpha}, -{beta}, but not RXR-{gamma}. Although ATRA was not effective in inhibiting proliferation or in inducing apoptosis in airway SMC, we found that ATRA (0.2 - 2 µM) inhibited the SMC migration in response to platelet-derived growth factor (PDGF) as determined in a modified Boyden chamber assay. Both RAR and RXR agonists also blocked PDGF-induced airway SMC migration. ATRA also inhibited PDGF-induced actin reorganization associated with migration. PDGF-induced actin reorganization and migration were blocked by inhibitors of PI-3 kinase and Akt. However, migration was blocked by inhibitors of the MEK/ERK pathway with no effect on cytoskeletal reorganization. ATRA suppressed PDGF-induced Akt activation without influencing ERK activation. RAR was found to form protein-protein interactions with the p85 PI-3 kinase subunit. These results suggest that retinoic acid inhibits airway SMC migration through the modulation of the PI-3 kinase/Akt pathway.




This article has been cited by other articles:


Home page
 J. Nutr.Home page
A. Harari, D. Harats, D. Marko, H. Cohen, I. Barshack, Y. Kamari, A. Gonen, Y. Gerber, A. Ben-Amotz, and A. Shaish
A 9-cis {beta}-Carotene-Enriched Diet Inhibits Atherogenesis and Fatty Liver Formation in LDL Receptor Knockout Mice
J. Nutr., October 1, 2008; 138(10): 1923 - 1930.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y. Ohta, M. Hayashi, T. Kanemaru, K. Abe, Y. Ito, and M. Oike
Dual Modulation of Airway Smooth Muscle Contraction by Th2 Cytokines via Matrix Metalloproteinase-1 Production
J. Immunol., March 15, 2008; 180(6): 4191 - 4199.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
W. T. Gerthoffer
Migration of Airway Smooth Muscle Cells
Proceedings of the ATS, January 1, 2008; 5(1): 97 - 105.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
C. J. Delvecchio, P. Bilan, K. Radford, J. Stephen, B. L. Trigatti, G. Cox, K. Parameswaran, and J. P. Capone
Liver X Receptor Stimulates Cholesterol Efflux and Inhibits Expression of Proinflammatory Mediators in Human Airway Smooth Muscle Cells
Mol. Endocrinol., June 1, 2007; 21(6): 1324 - 1334.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2006 American Thoracic Society. 		  2009 ATS Conference