help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on October 20, 2005, doi:10.1165/rcmb.2005-0166OC

Am. J. Respir. Cell Mol. Biol., Volume 34, Number 2, February 2006, 247-254

A more recent version of this article appeared on February 1, 2006
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2005-0166OCv1
34/2/247    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 Goldsmith, A. M
Right arrow Articles by Hershenson, M. B
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Goldsmith, A. M
Right arrow Articles by Hershenson, M. B

Submitted on May 2, 2005
Revised on October 19, 2005

Transforming Growth Factor-{beta} Induces Airway Smooth Muscle Hypertrophy

Adam M Goldsmith1, J. Kelley Bentley1, Limei Zhou1, Yue Jia1, Khalil N Bitar1, Diane C Fingar2, and Marc B Hershenson1*

1 Department of Pediatrics and Communicable Diseases and Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA, 2 Department of Cell and Developmental Biology and Department of Medicine, University of Michigan, Ann Arbor, MI, USA

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

Although smooth muscle hypertrophy is present in asthmatic airways, little is known about the biochemical pathways regulating airway smooth muscle protein synthesis, cell size or accumulation of contractile apparatus proteins. We sought to develop a model of airway smooth muscle hypertrophy in primary cells using a physiologically-relevant stimulus. We hypothesized that transforming growth factor-{beta} induces hypertrophy in primary bronchial smooth muscle cells. Primary human bronchial smooth muscle cells isolated from unacceptable lung donor tissue were studied. Cells were seeded on uncoated plastic dishes at 50% confluence and transforming growth factor-{beta} was added. Experiments were performed in the absence of serum. Transforming growth factor-{beta} increased cell size and total protein synthesis, expression of {alpha}-smooth muscle actin and smooth muscle myosin heavy chain, formation of actomyosin filaments, and cell shortening to acetylcholine. Further, transforming growth factor-{beta} increased airway smooth muscle {alpha}-actin synthesis in the presence of the transcriptional inhibitor actinomycin D, evidence that translational control is a physiologically important element of the observed hypertrophy. Transforming growth factor-{beta} induced the phosphorylation of eukaryotic translation initiation factor-4E-binding protein, a signaling event specifically involved in translational control. Finally, two inhibitors of 4E-binding protein phosphorylation, the phosphoinositol 3-kinase inhibitor LY294002 and a phosphorylation site mutant of 4E-binding protein-1 that dominantly inhibits eukaryotic initiation factor-4E, blocked transforming growth factor-{beta}-induced {alpha}-actin expression and cell enlargement. We conclude that transforming growth factor-{beta} induces hypertrophy of primary bronchial smooth muscle cells. Further, phosphorylation of 4E-binding protein is required for the observed hypertrophy.




This article has been cited by other articles:


Home page
 J. Immunol.Home page
L. Woodman, S. Siddiqui, G. Cruse, A. Sutcliffe, R. Saunders, D. Kaur, P. Bradding, and C. Brightling
Mast Cells Promote Airway Smooth Muscle Cell Differentiation via Autocrine Up-Regulation of TGF-{beta}1
J. Immunol., October 1, 2008; 181(7): 5001 - 5007.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
H. Meurs, R. Gosens, and J. Zaagsma
Airway hyperresponsiveness in asthma: lessons from in vitro model systems and animal models
Eur. Respir. J., August 1, 2008; 32(2): 487 - 502.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Deng, G. A. Dokshin, J. Lei, A. M. Goldsmith, K. N. Bitar, D. C. Fingar, M. B. Hershenson, and J. K. Bentley
Inhibition of Glycogen Synthase Kinase-3{beta} Is Sufficient for Airway Smooth Muscle Hypertrophy
J. Biol. Chem., April 11, 2008; 283(15): 10198 - 10207.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
A. J. Halayko, T. Tran, and R. Gosens
Phenotype and Functional Plasticity of Airway Smooth Muscle: Role of Caveolae and Caveolins
Proceedings of the ATS, January 1, 2008; 5(1): 80 - 88.
[Abstract] [Full Text] [PDF]

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
 Am. J. Respir. Cell Mol. Bio.Home page
T. Tran, K. Ens-Blackie, E. S. Rector, G. L. Stelmack, K. D. McNeill, G. Tarone, W. T. Gerthoffer, H. Unruh, and A. J. Halayko
Laminin-Binding Integrin {alpha}7 Is Required for Contractile Phenotype Expression by Human Airway Myocytes
Am. J. Respir. Cell Mol. Biol., December 1, 2007; 37(6): 668 - 680.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
H. Matsumoto, L. M Moir, B. G G Oliver, J. K Burgess, M. Roth, J. L Black, and B. E McParland
Comparison of gel contraction mediated by airway smooth muscle cells from patients with and without asthma
Thorax, October 1, 2007; 62(10): 848 - 854.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
S. Lamouille and R. Derynck
Cell size and invasion in TGF-{beta} induced epithelial to mesenchymal transition is regulated by activation of the mTOR pathway
J. Cell Biol., July 24, 2007; 178(3): 437 - 451.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. Xie, M. B. Sukkar, R. Issa, N. M. Khorasani, and K. F. Chung
Mechanisms of induction of airway smooth muscle hyperplasia by transforming growth factor-beta
Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L245 - L253.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. Sturrock, T. P. Huecksteadt, K. Norman, K. Sanders, T. M. Murphy, P. Chitano, K. Wilson, J. R. Hoidal, and T. P. Kennedy
Nox4 mediates TGF-beta1-induced retinoblastoma protein phosphorylation, proliferation, and hypertrophy in human airway smooth muscle cells
Am J Physiol Lung Cell Mol Physiol, June 1, 2007; 292(6): L1543 - L1555.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
E. D. Fixman, A. Stewart, and J. G. Martin
Basic mechanisms of development of airway structural changes in asthma
Eur. Respir. J., February 1, 2007; 29(2): 379 - 389.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. M. Goldsmith, M. B. Hershenson, M. P. Wolbert, and J. K. Bentley
Regulation of airway smooth muscle {alpha}-actin expression by glucocorticoids
Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L99 - L106.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2005 American Thoracic Society. 		  2009 ATS Conference