help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Published ahead of print on January 31, 2003, doi:10.1165/rcmb.2002-0254OC
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2002-0254OCv1
29/1/19    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 Goncharova, E. A.
Right arrow Articles by Panettieri, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Goncharova, E. A.
Right arrow Articles by Panettieri, R. A., Jr.
American Journal of Respiratory Cell and Molecular Biology. Vol. 29, pp. 19-27, 2003
© 2003 American Thoracic Society
DOI: 10.1165/rcmb.2002-0254OC

Cyclic AMP-Mobilizing Agents and Glucocorticoids Modulate Human Smooth Muscle Cell Migration

Elena A. Goncharova, Charlotte K. Billington, Carla Irani, Alexander V. Vorotnikov, Vsevolod A. Tkachuk, Raymond B. Penn, Vera P. Krymskaya and Reynold A. Panettieri, Jr.

Pulmonary, Allergy, and Critical Care Division, Department of Medicine, University of Pennsylvania; Division of Critical Care, Pulmonary, Allergic & Immunologic Diseases, Jefferson Medical College, and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania; and Laboratory of Cell Motility, Laboratory of Molecular Endocrinology, Institute of Experimental Cardiology, Russian Cardiology Research Center, Moscow, Russia

Address correspondence to: Reynold A. Panettieri, Jr., M.D., Pulmonary, Allergy and Critical Care Division, University of Pennsylvania, 421 Curie Boulevard, Room 805 BRB II/III, Philadelphia, PA 19104-6160. E-mail: rap{at}mail.med.upenn.edu

Hyperplasia and cell migration of smooth muscle are features of both airway and pulmonary vascular diseases. The precise cellular and molecular mechanisms that regulate smooth muscle migration in the lungs remain unknown. In this study, we examined the effect of cAMP-mobilizing agents and steroids on smooth muscle cell migration. Platelet-derived growth factor (PDGF), transforming growth factor-{alpha}, vascular endothelial growth factor, and basic fibroblast growth factor significantly stimulated cell migration in pulmonary vascular smooth muscle (PVSM) cells. Airway smooth muscle (ASM) migration was also stimulated by PDGF, transforming growth factor-{alpha}, and basic fibroblast growth factor, but vascular endothelial growth factor was without effect. Interestingly, the smooth muscle mitogen thrombin did not stimulate migration of either cell type. Agents capable of elevating intracellular cAMP inhibited basal (unstimulated) cell migration in both cell types, whereas their effects on PDGF-stimulated migration were more variable. Prostaglandin E2, salmeterol, and the phosphodiesterase type 4 inhibitor cilomolast inhibited basal ASM and PVSM migration by 30–60%. Prostaglandin E2 and cilomolast also inhibited PDGF-stimulated migration of ASM and PVSM cells, but salmeterol was without effect. Preincubation of ASM cells with dexamethasone or fluticasone inhibited basal and PDGF-stimulated migration, and enabled an inhibitory effect of salmeterol on PDGF-induced cell migration. Steroids alone did not stimulate cAMP production or cAMP/PKA-dependent gene transcription (CRE-Luc activity), but slightly augmented salmeterol-stimulated CRE-Luc activity. Collectively, these findings demonstrate that cAMP-mobilizing agents and steroids modulate human smooth muscle cell migration, likely by distinct mechanisms.

Abbreviations: airway smooth muscle, ASM • basic fibroblast growth factor, bFGF • cAMP/PKA-dependent gene transcription, CRE-Luc activity • fetal bovine serum, FBS • phosphodiesterase type 4, PDE4 • platelet-derived growth factor, PDGF • prostaglandin E2, PGE2 • pulmonary vascular smooth muscle, PVSM • transforming growth factor-{alpha}, TGF-{alpha} • vascular endothelial growth factor, VEGF




This article has been cited by other articles:


Home page
 Proc Am Thorac SocHome page
J. K. Bentley and M. B. Hershenson
Airway Smooth Muscle Growth in Asthma: Proliferation, Hypertrophy, and Migration
Proceedings of the ATS, January 1, 2008; 5(1): 89 - 96.
[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
 Eur J EndocrinolHome page
B. R Walker
Glucocorticoids and Cardiovascular Disease
Eur. J. Endocrinol., November 1, 2007; 157(5): 545 - 559.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
E. H. Walters, D. W. Reid, D. P. Johns, and C. Ward
Nonpharmacological and pharmacological interventions to prevent or reduce airway remodelling
Eur. Respir. J., September 1, 2007; 30(3): 574 - 588.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
K. Parameswaran, K. Radford, A. Fanat, J. Stephen, C. Bonnans, B. D. Levy, L. J. Janssen, and P. G. Cox
Modulation of Human Airway Smooth Muscle Migration by Lipid Mediators and Th-2 Cytokines
Am. J. Respir. Cell Mol. Biol., August 1, 2007; 37(2): 240 - 247.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. Hirakawa, Y. Karashima, M. Watanabe, C. Kimura, Y. Ito, and M. Oike
Protein Kinase A Inhibits Lysophosphatidic Acid-Induced Migration of Airway Smooth Muscle Cells
J. Pharmacol. Exp. Ther., June 1, 2007; 321(3): 1102 - 1108.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
Y. Osawa, P. D. Yim, D. Xu, R. A. Panettieri, and C. W. Emala
Raf-1 kinase mediates adenylyl cyclase sensitization by TNF-{alpha} in human airway smooth muscle cells
Am J Physiol Lung Cell Mol Physiol, June 1, 2007; 292(6): L1414 - L1421.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
S. Jalvy, M.-A. Renault, L. Lam Shang Leen, I. Belloc, A. Reynaud, A.-P. Gadeau, and C. Desgranges
CREB Mediates UTP-Directed Arterial Smooth Muscle Cell Migration and Expression of the Chemotactic Protein Osteopontin via Its Interaction with Activator Protein-1 Sites
Circ. Res., May 11, 2007; 100(9): 1292 - 1299.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
S. S. An, T. R. Bai, J. H. T. Bates, J. L. Black, R. H. Brown, V. Brusasco, P. Chitano, L. Deng, M. Dowell, D. H. Eidelman, et al.
Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma
Eur. Respir. J., May 1, 2007; 29(5): 834 - 860.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. Zhang, H. H. Patel, F. Murray, C. V. Remillard, C. Schach, P. A. Thistlethwaite, Paul. A. Insel, and J. X.-J. Yuan
Pulmonary artery smooth muscle cells from normal subjects and IPAH patients show divergent cAMP-mediated effects on TRPC expression and capacitative Ca2+ entry
Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1202 - L1210.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
E. A. Goncharova, D. A. Goncharov, P. N. Lim, D. Noonan, and V. P. Krymskaya
Modulation of Cell Migration and Invasiveness by Tumor Suppressor TSC2 in Lymphangioleiomyomatosis
Am. J. Respir. Cell Mol. Biol., April 1, 2006; 34(4): 473 - 480.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
K. F. Chung
The Role of Airway Smooth Muscle in the Pathogenesis of Airway Wall Remodeling in Chronic Obstructive Pulmonary Disease
Proceedings of the ATS, November 1, 2005; 2(4): 347 - 354.
[Abstract] [Full Text] [PDF]

Home page
 Sci SignalHome page
K. F. Chung
Evaluation of Selective Prostaglandin E2 (PGE2) Receptor Agonists as Therapeutic Agents for the Treatment of Asthma
Sci. Signal., September 27, 2005; 2005(303): pe47 - pe47.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
P. Joubert, S. Lajoie-Kadoch, I. Labonte, A. S. Gounni, K. Maghni, V. Wellemans, J. Chakir, M. Laviolette, Q. Hamid, and B. Lamkhioued
CCR3 Expression and Function in Asthmatic Airway Smooth Muscle Cells
J. Immunol., August 15, 2005; 175(4): 2702 - 2708.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Naik, C. K. Billington, R. M. Pascual, D. A. Deshpande, F. P. Stefano, T. A. Kohout, D. M. Eckman, J. L. Benovic, and R. B. Penn
Regulation of Cysteinyl Leukotriene Type 1 Receptor Internalization and Signaling
J. Biol. Chem., March 11, 2005; 280(10): 8722 - 8732.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
C. Bulin, U. Albrecht, J.G. Bode, A.-A. Weber, K. Schror, B. Levkau, and J.W. Fischer
Differential Effects of Vasodilatory Prostaglandins on Focal Adhesions, Cytoskeletal Architecture, and Migration in Human Aortic Smooth Muscle Cells
Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 84 - 89.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
A.G. Stewart
Emigration and immigration of mesenchymal cells: a multicultural airway wall
Eur. Respir. J., October 1, 2004; 24(4): 515 - 517.
[Full Text] [PDF]

Home page
 Eur Respir JHome page
K. Parameswaran, K. Radford, J. Zuo, L.J. Janssen, P.M. O'Byrne, and P.G. Cox
Extracellular matrix regulates human airway smooth muscle cell migration
Eur. Respir. J., October 1, 2004; 24(4): 545 - 551.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
J. M. Madison
Migration of Airway Smooth Muscle Cells
Am. J. Respir. Cell Mol. Biol., July 1, 2003; 29(1): 8 - 11.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2003 American Thoracic Society.