AJP - Lung AJP citation statistics
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Lung Cell Mol Physiol (October 8, 2004). doi:10.1152/ajplung.00213.2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
288/2/L294    most recent
00213.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Clements, R. T.
Right arrow Articles by Vincent, P. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Clements, R. T.
Right arrow Articles by Vincent, P. A.
Submitted on June 8, 2004
Accepted on October 5, 2004

RhoA AND Rho-KINASE DEPENDENT AND INDEPENDENT SIGNALS MEDIATETGF{beta}-INDUCED PULMONARY ENDOTHELIAL CYTOSKELETAL REORGANIZATION AND PERMEABILITY

Richard T. Clements1, Fred L. Minnear2, Harold A. Singer1, Rebecca S. Keller1, and Peter A. Vincent1*

1 Center for Cardiovascular Sciences, Albany Medical College, Albany, NY, USA
2 West Virginia University, Morgantown, WV, USA

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

Transforming Growth Factor {beta} (TGF{beta}) is a potent inflammatory mediator involved in acute lung injury. TGF{beta} directly increases pulmonary endothelial myosin light chain (MLC) phosphorylation which is associated with increased endothelial stress fiber formation, gap formation, and protein permeability; all hallmarks of pulmonary endothelial responses during acute lung injury. We performed the following experiments in pulmonary endothelial monolayers to determine if RhoA and Rho-kinase mediate these TGF{beta}-induced responses. TGF{beta} caused the sustained activation of RhoA two hours post treatment that associated with increased MLC phosphorylation. Inhibition of either RhoA or Rho-kinase with either C3 -exoenzyme or Y27632 blocked MLC phosphorylation. In addition both C3 and Y27632 partially attenuated the maximal TGF{beta}-induced increase in permeability, but did not affect the initial phase of compromised barrier integrity. Inhibition of Rho-kinase completely blocked the TGF{beta}-induced increase in the content of filamentous actin (f-actin), but only partially inhibited TGF{beta}-induced changes in actin reorganization. To assess the contribution of Rho-kinase in RhoA mediated responses independent of additional TGF{beta}-induced signals, cells were infected with a constitutively active RhoA adenovirus (RhoAQ63L) with or without Y27632. RhoAQ63L increased MLC phosphorylation, f-actin content, and permeability. Treatment with Y27632 blocked these responses, suggesting that Rho-kinase mediates these RhoA-induced effects. Collectively, these data suggest the following: 1) the RhoA/Rho-kinase pathway is an important component of TGF{beta}-induced effects on endothelial MLC phosphorylation, cytoskeletal reorganization, and barrier integrity; and 2) additional signaling mechanisms independent of the RhoA/Rho-kinase signaling cascade contribute to TGF{beta}-induced changes in cytoskeletal organization and permeability.




This article has been cited by other articles:


Home page
 Cancer Res.Home page
R. M. Klein and A. E. Aplin
Rnd3 Regulation of the Actin Cytoskeleton Promotes Melanoma Migration and Invasive Outgrowth in Three Dimensions
Cancer Res., March 15, 2009; 69(6): 2224 - 2233.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
M. Guo, D. Daines, J. Tang, Q. Shen, R. M. Perrin, Y. Takada, S. Y. Yuan, and M. H. Wu
Fibrinogen-{gamma} C-Terminal Fragments Induce Endothelial Barrier Dysfunction and Microvascular Leak via Integrin-Mediated and RhoA-Dependent Mechanism
Arterioscler Thromb Vasc Biol, March 1, 2009; 29(3): 394 - 400.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
D. Xing and J. A. Bonanno
Effect of cAMP on TGF{beta}1-Induced Corneal Keratocyte-Myofibroblast Transformation
Invest. Ophthalmol. Vis. Sci., February 1, 2009; 50(2): 626 - 633.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
A. Antonov, C. Snead, B. Gorshkov, G. N. Antonova, A. D. Verin, and J. D. Catravas
Heat Shock Protein 90 Inhibitors Protect and Restore Pulmonary Endothelial Barrier Function
Am. J. Respir. Cell Mol. Biol., November 1, 2008; 39(5): 551 - 559.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
G. P. van Nieuw Amerongen, R. J. P. Musters, E. C. Eringa, P. Sipkema, and V. W. M. van Hinsbergh
Thrombin-induced endothelial barrier disruption in intact microvessels: role of RhoA/Rho kinase-myosin phosphatase axis
Am J Physiol Cell Physiol, May 1, 2008; 294(5): C1234 - C1241.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
M. T. Ganter, J. Roux, B. Miyazawa, M. Howard, J. A. Frank, G. Su, D. Sheppard, S. M. Violette, P. H. Weinreb, G. S. Horan, et al.
Interleukin-1{beta} Causes Acute Lung Injury via {alpha}v{beta}5 and {alpha}v{beta}6 Integrin-Dependent Mechanisms
Circ. Res., April 11, 2008; 102(7): 804 - 812.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
Y. H. Lee, U. S. Kayyali, A. M. Sousa, T. Rajan, R. J. Lechleider, and R. M. Day
Transforming Growth Factor-beta1 Effects on Endothelial Monolayer Permeability Involve Focal Adhesion Kinase/Src
Am. J. Respir. Cell Mol. Biol., October 1, 2007; 37(4): 485 - 493.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
D. Singh, K. L. McCann, and F. Imani
MAPK and heat shock protein 27 activation are associated with respiratory syncytial virus induction of human bronchial epithelial monolayer disruption
Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L436 - L445.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
M. Carlile-Klusacek and V. Rizzo
Endothelial cytoskeletal reorganization in response to PAR1 stimulation is mediated by membrane rafts but not caveolae
Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H366 - H375.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
G. Su, M. Hodnett, N. Wu, A. Atakilit, C. Kosinski, M. Godzich, X. Z. Huang, J. K. Kim, J. A. Frank, M. A. Matthay, et al.
Integrin {alpha}vbeta5 Regulates Lung Vascular Permeability and Pulmonary Endothelial Barrier Function
Am. J. Respir. Cell Mol. Biol., March 1, 2007; 36(3): 377 - 386.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
D. M. Guidot, H. G. Folkesson, L. Jain, J. I. Sznajder, J.-F. Pittet, and M. A. Matthay
Integrating acute lung injury and regulation of alveolar fluid clearance
Am J Physiol Lung Cell Mol Physiol, September 1, 2006; 291(3): L301 - L306.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
Q. Lu, E. O. Harrington, H. Jackson, N. Morin, C. Shannon, and S. Rounds
Transforming growth factor-beta1-induced endothelial barrier dysfunction involves Smad2-dependent p38 activation and subsequent RhoA activation
J Appl Physiol, August 1, 2006; 101(2): 375 - 384.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J. Qiao, F. Huang, R. P. Naikawadi, K. S. Kim, T. Said, and H. Lum
Lysophosphatidylcholine impairs endothelial barrier function through the G protein-coupled receptor GPR4
Am J Physiol Lung Cell Mol Physiol, July 1, 2006; 291(1): L91 - L101.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. Moldobaeva, L. E. Welsh-Servinsky, L. A. Shimoda, R. S. Stephens, A. D. Verin, R. M. Tuder, and D. B. Pearse
Role of protein kinase G in barrier-protective effects of cGMP in human pulmonary artery endothelial cells
Am J Physiol Lung Cell Mol Physiol, May 1, 2006; 290(5): L919 - L930.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. W. Breslin, H. Sun, W. Xu, C. Rodarte, A. B. Moy, M. H. Wu, and S. Y. Yuan
Involvement of ROCK-mediated endothelial tension development in neutrophil-stimulated microvascular leakage
Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H741 - H750.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 2004 by the American Physiological Society.