AJP - Heart AJP: Cell Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 285: H1871-H1881, 2003. First published July 3, 2003; doi:10.1152/ajpheart.00387.2003
0363-6135/03 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
285/5/H1871    most recent
00387.2003v1
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 HighWire
Right arrow Citing Articles via Web of Science (46)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wang, J.
Right arrow Articles by McCulloch, C. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, J.
Right arrow Articles by McCulloch, C. A.

Mechanical force regulation of myofibroblast differentiation in cardiac fibroblasts

J. Wang, H. Chen, A. Seth, and C. A. McCulloch

Canadian Institutes of Health Research Group in Matrix Dynamics, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada M5S 3E8

Submitted 25 April 2003 ; accepted in final form 25 June 2003

The myocardium responds to chronic pressure or volume overload by activation and proliferation of cardiac fibroblasts and their differentiation into myofibroblasts. Because {alpha}-smooth muscle actin (SMA) expression is the classical marker for myofibroblast differentiation, we examined force-induced SMA expression and regulation by specific MAPK pathways. Rat cardiac fibroblasts were separated from myocytes and smooth muscle cells, cultured, and phenotyped by using the presence of SMA, vimentin, and ED-A fibronectin and the absence of desmin as myofibroblast markers. Static tensile forces (0.65 pN/µm2) were applied to fibroblasts via collagen-coated magnetite beads. In neonatal cardiac fibroblasts cultured for 1 day, immunostaining and Western and Northern blotting showed very low basal levels of SMA. After the application of force, there were 1.5- to 2-fold increases of SMA protein and mRNA within 4 h. Force-induced SMA expression was dependent on ERK phosphorylation and on intact actin filaments. In contrast to cells cultured for 1 day, cells grown for 3 days on rigid substrates showed prominent stress fibers and high basal levels of SMA, which were reduced by 32% within 4 h after force application. ERK was not activated by force, but p38 phosphorylation was required for force-induced inhibition of SMA expression. These results indicate that mechanical force-induced regulation of SMA content is dependent on myofibroblast differentiation and by selective activation of MAPKs.

force application; integrins; cell differentiation; extracellular signal-regulated kinase; p38


Address for reprint requests and other correspondence: C. A. McCulloch, Rm. 244, Fitzgerald Bldg., Univ. of Toronto, 150 College St., Toronto, Ontario, Canada M5S 3E8 (E-mail: christopher.mcculloch{at}utoronto.ca).




This article has been cited by other articles:


Home page
 J. Cell Sci.Home page
M. W. C. Chan, P. D. Arora, P. Bozavikov, and C. A. McCulloch
FAK, PIP5KI{gamma} and gelsolin cooperatively mediate force-induced expression of {alpha}-smooth muscle actin
J. Cell Sci., August 1, 2009; 122(15): 2769 - 2781.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
L. C. McSpadden, R. D. Kirkton, and N. Bursac
Electrotonic loading of anisotropic cardiac monolayers by unexcitable cells depends on connexin type and expression level
Am J Physiol Cell Physiol, August 1, 2009; 297(2): C339 - C351.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
K. Vaahtomeri, E. Ventela, K. Laajanen, P. Katajisto, P.-J. Wipff, B. Hinz, T. Vallenius, M. Tiainen, and T. P. Makela
Lkb1 is required for TGF{beta}-mediated myofibroblast differentiation
J. Cell Sci., November 1, 2008; 121(21): 3531 - 3540.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
V. Drobic, R. H. Cunnington, K. M. Bedosky, J. E. Raizman, V. V. Elimban, S. G. Rattan, and I. M. C. Dixon
Differential and combined effects of cardiotrophin-1 and TGF-beta1 on cardiac myofibroblast proliferation and contraction
Am J Physiol Heart Circ Physiol, August 1, 2007; 293(2): H1053 - H1064.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
B. E.J. Teunissen, P. J.H. Smeets, P. H.M. Willemsen, L. J. De Windt, G. J. Van der Vusse, and M. Van Bilsen
Activation of PPAR{delta} inhibits cardiac fibroblast proliferation and the transdifferentiation into myofibroblasts
Cardiovasc Res, August 1, 2007; 75(3): 519 - 529.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
Z. Jiang, P. Yu, M. Tao, C. Fernandez, C. Ifantides, O. Moloye, G. S. Schultz, C. K. Ozaki, and S. A. Berceli
TGF-beta- and CTGF-mediated fibroblast recruitment influences early outward vein graft remodeling
Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H482 - H488.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
X.-H. Zhao, C. Laschinger, P. Arora, K. Szaszi, A. Kapus, and C. A. McCulloch
Force activates smooth muscle {alpha}-actin promoter activity through the Rho signaling pathway
J. Cell Sci., May 15, 2007; 120(10): 1801 - 1809.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
Y. Onai, J.-i. Suzuki, Y. Maejima, G. Haraguchi, S. Muto, A. Itai, and M. Isobe
Inhibition of NF-{kappa}B improves left ventricular remodeling and cardiac dysfunction after myocardial infarction
Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H530 - H538.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
F. Poobalarahi, C. F. Baicu, and A. D. Bradshaw
Cardiac myofibroblasts differentiated in 3D culture exhibit distinct changes in collagen I production, processing, and matrix deposition
Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2924 - H2932.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
M. Miragoli, G. Gaudesius, and S. Rohr
Electrotonic Modulation of Cardiac Impulse Conduction by Myofibroblasts
Circ. Res., March 31, 2006; 98(6): 801 - 810.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. E. Naugle, E. R. Olson, X. Zhang, S. E. Mase, C. F. Pilati, M. B. Maron, H. G. Folkesson, W. I. Horne, K. J. Doane, and J. G. Meszaros
Type VI collagen induces cardiac myofibroblast differentiation: implications for postinfarction remodeling
Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H323 - H330.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
L. Chilton, S. Ohya, D. Freed, E. George, V. Drobic, Y. Shibukawa, K. A. MacCannell, Y. Imaizumi, R. B. Clark, I. M. C. Dixon, et al.
K+ currents regulate the resting membrane potential, proliferation, and contractile responses in ventricular fibroblasts and myofibroblasts
Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2931 - H2939.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
H. Shiratsuchi and M. D. Basson
Activation of p38 MAPK{alpha} by extracellular pressure mediates the stimulation of macrophage phagocytosis by pressure
Am J Physiol Cell Physiol, May 1, 2005; 288(5): C1083 - C1093.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
H. Shiratsuchi and M. D. Basson
Extracellular pressure stimulates macrophage phagocytosis by inhibiting a pathway involving FAK and ERK
Am J Physiol Cell Physiol, June 1, 2004; 286(6): C1358 - C1366.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2003 by the American Physiological Society.