| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
-Smooth Muscle Actin in Fibroblasts
From the MRC Group In Periodontal Physiology, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada
Wound contraction is mediated by myofibroblasts,
specialized fibroblasts that appear in large numbers as the wound
matures and when resistance to contractile forces increases. We
considered that the regulation of myofibroblast differentiation by
wound-healing cytokines may be dependent on the resistance of the
connective tissue matrix to deformation. We examined transforming
growth factor-ß1 (TGF-ß1) induction of the
putative fibroblast contractile marker, 
-smooth muscle actin
(-SMA), and the regulation of this process by the compliance
of collagen substrates. Cells were cultured in three different types of
collagen gels with wide variations of mechanical compliance as assessed
by deformation testing. The resistance to collagen gel deformation
determined the levels of intracellular tension as shown by staining for
actin stress fibers. For cells plated on thin films of collagen-coated
plastic (ie, minimal compliance and maximal intracellular
tension), TGF-ß1 (10 ng/ml; 6 days) increased
-SMA protein content by ninefold as detected by Western blots but
did not affect ß-actin content. Western blots of cells in anchored
collagen gels (moderate compliance and tension) also showed a
TGF-ß1-induced increase of -SMA content, but
the effect was greatly reduced compared with collagen-coated plastic
(<3-fold increase). In floating collagen gels (high compliance and low
tension), there were only minimal differences of -SMA
protein. Northern analyses for -SMA and ß-actin indicated that
TGF-ß1 selectively increased mRNA for -SMA similar to
the reported protein levels. In pulse-chase experiments,
[35S]methionine-labeled intracellular -SMA decayed
most rapidly in floating gels, less rapidly in anchored
gels, and not at all in collagen plates after
TGF-ß1 treatment. TGF-ß1 increased
2 and ß1 integrin content by 50% in cells
on collagen plates, but the increase was less marked on
anchored gels and was undetectable in floating gels. When intracellular
tension on collagen substrates was reduced by preincubating cells with
blocking antibodies to the 2 and ß1
integrin subunits, TGF-ß1 failed to increase
-SMA protein content in all three types of collagen matrices. These
data indicate that TGF-ß1-induced increases of -SMA
content are dependent on the resistance of the substrate to deformation
and that the generation of intracellular tension is a central
determinant of contractile cytoskeletal gene expression.
This article has been cited by other articles:
 |
|
 |
|
  E. A. Sander, T. Stylianopoulos, R. T. Tranquillo, and V. H. Barocas Image-based multiscale modeling predicts tissue-level and network-level fiber reorganization in stretched cell-compacted collagen gels PNAS, October 20, 2009; 106(42): 17675 - 17680. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G Farina, R Lemaire, P Pancari, J Bayle, R L Widom, and R Lafyatis Cartilage oligomeric matrix protein expression in systemic sclerosis reveals heterogeneity of dermal fibroblast responses to transforming growth factor {beta} Ann Rheum Dis, March 1, 2009; 68(3): 435 - 441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. D. Arora, M. A. Conti, S. Ravid, D. B. Sacks, A. Kapus, R. S. Adelstein, A. R. Bresnick, and C. A. McCulloch Rap1 Activation in Collagen Phagocytosis Is Dependent on Nonmuscle Myosin II-A Mol. Biol. Cell, December 1, 2008; 19(12): 5032 - 5046. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Leask, X. Shi-wen, K. Khan, Y. Chen, A. Holmes, M. Eastwood, C. P. Denton, C. M. Black, and D. J. Abraham Loss of protein kinase C{epsilon} results in impaired cutaneous wound closure and myofibroblast function J. Cell Sci., October 15, 2008; 121(20): 3459 - 3467. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Patwari and R. T. Lee Mechanical Control of Tissue Morphogenesis Circ. Res., August 1, 2008; 103(3): 234 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Pho, W. Lee, D. R. Watt, C. Laschinger, C. A. Simmons, and C. A. McCulloch Cofilin is a marker of myofibroblast differentiation in cells from porcine aortic cardiac valves Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1767 - H1778. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. G. Wells and D. E. Discher Matrix Elasticity, Cytoskeletal Tension, and TGF-{beta}: The Insoluble and Soluble Meet Sci. Signal., March 11, 2008; 1(10): pe13 - pe13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Lenga, A. Koh, A. S. Perera, C. A. McCulloch, J. Sodek, and R. Zohar Osteopontin Expression Is Required for Myofibroblast Differentiation Circ. Res., February 15, 2008; 102(3): 319 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.-J. Wipff, D. B. Rifkin, J.-J. Meister, and B. Hinz Myofibroblast contraction activates latent TGF- 1 from the extracellular matrix J. Cell Biol., December 17, 2007; 179(6): 1311 - 1323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Ferdous, V. M. Wei, R. Iozzo, M. Hook, and K. J. Grande-Allen Decorin-transforming Growth Factor- Interaction Regulates Matrix Organization and Mechanical Characteristics of Three-dimensional Collagen Matrices J. Biol. Chem., December 7, 2007; 282(49): 35887 - 35898. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. C. Georges, J.-J. Hui, Z. Gombos, M. E. McCormick, A. Y. Wang, M. Uemura, R. Mick, P. A. Janmey, E. E. Furth, and R. G. Wells Increased stiffness of the rat liver precedes matrix deposition: implications for fibrosis Am J Physiol Gastrointest Liver Physiol, December 1, 2007; 293(6): G1147 - G1154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Liu, R. R. Warburton, O. E. Guevara, N. S. Hill, B. L. Fanburg, M. Gaestel, and U. S. Kayyali Lack of MK2 Inhibits Myofibroblast Formation and Exacerbates Pulmonary Fibrosis Am. J. Respir. Cell Mol. Biol., November 1, 2007; 37(5): 507 - 517. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 T. Meyer-ter-Vehn, S. Sieprath, B. Katzenberger, S. Gebhardt, F. Grehn, and G. Schlunck Contractility as a Prerequisite for TGF-{beta}-Induced Myofibroblast Transdifferentiation in Human Tenon Fibroblasts Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 4895 - 4904. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Araya, S. Cambier, A. Morris, W. Finkbeiner, and S. L. Nishimura Integrin-Mediated Transforming Growth Factor-{beta} Activation Regulates Homeostasis of the Pulmonary Epithelial-Mesenchymal Trophic Unit Am. J. Pathol., August 1, 2006; 169(2): 405 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. R. Arany, K. C. Flanders, T. Kobayashi, C. K. Kuo, C. Stuelten, K. V. Desai, R. Tuan, S. I. Rennard, and A. B. Roberts Smad3 deficiency alters key structural elements of the extracellular matrix and mechanotransduction of wound closure PNAS, June 13, 2006; 103(24): 9250 - 9255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Meyer-ter-Vehn, S. Gebhardt, W. Sebald, M. Buttmann, F. Grehn, G. Schlunck, and P. Knaus p38 Inhibitors Prevent TGF-{beta}-Induced Myofibroblast Transdifferentiation in Human Tenon Fibroblasts. Invest. Ophthalmol. Vis. Sci., April 1, 2006; 47(4): 1500 - 1509. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Goffin, P. Pittet, G. Csucs, J. W. Lussi, J.-J. Meister, and B. Hinz Focal adhesion size controls tension-dependent recruitment of {alpha}-smooth muscle actin to stress fibers J. Cell Biol., January 16, 2006; 172(2): 259 - 268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. J. Thannickal and J. C. Horowitz Evolving concepts of apoptosis in idiopathic pulmonary fibrosis. Proceedings of the ATS, January 1, 2006; 3(4): 350 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P. Ng, B. Hinz, and M. A. Swartz Interstitial fluid flow induces myofibroblast differentiation and collagen alignment in vitro J. Cell Sci., October 15, 2005; 118(20): 4731 - 4739. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.E. van Beurden, J.W. Von den Hoff, R. Torensma, J.C. Maltha, and A.M. Kuijpers-Jagtman Myofibroblasts in Palatal Wound Healing: Prospects for the Reduction of Wound Contraction after Cleft Palate Repair Journal of Dental Research, October 1, 2005; 84(10): 871 - 880. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. C. Georges and P. A. Janmey Cell type-specific response to growth on soft materials J Appl Physiol, April 1, 2005; 98(4): 1547 - 1553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wang, J. Fan, C. Laschinger, P. D. Arora, A. Kapus, A. Seth, and C. A. McCulloch Smooth Muscle Actin Determines Mechanical Force-induced p38 Activation J. Biol. Chem., February 25, 2005; 280(8): 7273 - 7284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Swaney, D. M. Roth, E. R. Olson, J. E. Naugle, J. G. Meszaros, and P. A. Insel Inhibition of cardiac myofibroblast formation and collagen synthesis by activation and overexpression of adenylyl cyclase PNAS, January 11, 2005; 102(2): 437 - 442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Tornblom, F. A. Patel, B. Bystrom, D. Giannoulias, A. Malmstrom, M. Sennstrom, S. J. Lye, J. R. G. Challis, and G. Ekman 15-Hydroxyprostaglandin Dehydrogenase and Cyclooxygenase 2 Messenger Ribonucleic Acid Expression and Immunohistochemical Localization in Human Cervical Tissue during Term and Preterm Labor J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2909 - 2915. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Shephard, G. Martin, S. Smola-Hess, G. Brunner, T. Krieg, and H. Smola Myofibroblast Differentiation Is Induced in Keratinocyte-Fibroblast Co-Cultures and Is Antagonistically Regulated by Endogenous Transforming Growth Factor-{beta} and Interleukin-1 Am. J. Pathol., June 1, 2004; 164(6): 2055 - 2066. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Garrett, P. T. Khaw, T. D. Blalock, G. S. Schultz, G. R. Grotendorst, and J. T. Daniels Involvement of CTGF in TGF-{beta}1-Stimulation of Myofibroblast Differentiation and Collagen Matrix Contraction in the Presence of Mechanical Stress Invest. Ophthalmol. Vis. Sci., April 1, 2004; 45(4): 1109 - 1116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sukotjo, A. Lin, K. Song, T. Ogawa, B. Wu, and I. Nishimura Oral Fibroblast Expression of wound-inducible transcript 3.0 (wit3.0) Accelerates the Collagen Gel Contraction in Vitro J. Biol. Chem., December 19, 2003; 278(51): 51527 - 51534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Guo and L. Piacentini Type I Collagen-induced MMP-2 Activation Coincides with Up-regulation of Membrane Type 1-Matrix Metalloproteinase and TIMP-2 in Cardiac Fibroblasts J. Biol. Chem., November 21, 2003; 278(47): 46699 - 46708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Vishwanath, L. Ma, C. A. Otey, J. V. Jester, and W. M. Petroll Modulation of Corneal Fibroblast Contractility within Fibrillar Collagen Matrices Invest. Ophthalmol. Vis. Sci., November 1, 2003; 44(11): 4724 - 4735. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wang, H. Chen, A. Seth, and C. A. McCulloch Mechanical force regulation of myofibroblast differentiation in cardiac fibroblasts Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H1871 - H1881. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Lijnen, V. Petrov, and R. Fagard Transforming growth factor-{beta}1-mediated collagen gel contraction by cardiac fibroblasts Journal of Renin-Angiotensin-Aldosterone System, June 1, 2003; 4(2): 113 - 118. [Abstract] [PDF]
|
|
|
|
|
|
B. Hinz, V. Dugina, C. Ballestrem, B. Wehrle-Haller, and C. Chaponnier {alpha}-Smooth Muscle Actin Is Crucial for Focal Adhesion Maturation in Myofibroblasts Mol. Biol. Cell, June 1, 2003; 14(6): 2508 - 2519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ferri, K. J. Garton, and E. W. Raines An NF-{kappa}B-dependent Transcriptional Program Is Required for Collagen Remodeling by Human Smooth Muscle Cells J. Biol. Chem., May 23, 2003; 278(22): 19757 - 19764. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. J. Thannickal, D. Y. Lee, E. S. White, Z. Cui, J. M. Larios, R. Chacon, J. C. Horowitz, R. M. Day, and P. E. Thomas Myofibroblast Differentiation by Transforming Growth Factor-beta 1 Is Dependent on Cell Adhesion and Integrin Signaling via Focal Adhesion Kinase J. Biol. Chem., March 28, 2003; 278(14): 12384 - 12389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kim, X. Liu, T. Kobayashi, T. Kohyama, F.-Q. Wen, D. J. Romberger, H. Conner, P. S. Gilmour, K. Donaldson, W. MacNee, et al. Ultrafine Carbon Black Particles Inhibit Human Lung Fibroblast-Mediated Collagen Gel Contraction Am. J. Respir. Cell Mol. Biol., January 1, 2003; 28(1): 111 - 121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Phipps, S. Ying, A. Wangoo, Y.-E. Ong, F. Levi-Schaffer, and A. B. Kay The Relationship Between Allergen-Induced Tissue Eosinophilia and Markers of Repair and Remodeling in Human Atopic Skin J. Immunol., October 15, 2002; 169(8): 4604 - 4612. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Hinz, G. Gabbiani, and C. Chaponnier The NH2-terminal peptide of {alpha}-smooth muscle actin inhibits force generation by the myofibroblast in vitro and in vivo J. Cell Biol., May 13, 2002; 157(4): 657 - 663. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Hinz, D. Mastrangelo, C. E. Iselin, C. Chaponnier, and G. Gabbiani Mechanical Tension Controls Granulation Tissue Contractile Activity and Myofibroblast Differentiation Am. J. Pathol., September 1, 2001; 159(3): 1009 - 1020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Hinz, G. Celetta, J. J. Tomasek, G. Gabbiani, and C. Chaponnier Alpha-Smooth Muscle Actin Expression Upregulates Fibroblast Contractile Activity Mol. Biol. Cell, September 1, 2001; 12(9): 2730 - 2741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Abe, S. C. Donnelly, T. Peng, R. Bucala, and C. N. Metz Peripheral Blood Fibrocytes: Differentiation Pathway and Migration to Wound Sites J. Immunol., June 15, 2001; 166(12): 7556 - 7562. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Chegini, K. Kotseos, Y. Zhao, B. Bennett, F. W. McLean, M. P. Diamond, L. Holmdahl, and J. Burns Differential expression of TGF-{beta}1 and TGF-{beta}3 in serosal tissues of human intraperitoneal organs and peritoneal adhesions Hum. Reprod., June 1, 2001; 16(6): 1291 - 1300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Chen, Y. Wei, G. C. Sharp, and H. Braley-Mullen Characterization of thyroid fibrosis in a murine model of granulomatous experimental autoimmune thyroiditis J. Leukoc. Biol., December 1, 2000; 68(6): 828 - 835. [Abstract] [Full Text]
|
|
|
|
|
|
J. Wang, A. Seth, and C. A. G. McCulloch Force regulates smooth muscle actin in cardiac fibroblasts Am J Physiol Heart Circ Physiol, December 1, 2000; 279(6): H2776 - H2785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. D. Arora and C. A. G. McCulloch The Deletion of Transforming Growth Factor-{beta}-Induced Myofibroblasts Depends on Growth Conditions and Actin Organization Am. J. Pathol., December 1, 1999; 155(6): 2087 - 2099. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Larios, R. Budhiraja, B. L. Fanburg, and V. J. Thannickal Oxidative Protein Cross-linking Reactions Involving L-Tyrosine in Transforming Growth Factor-beta 1-stimulated Fibroblasts J. Biol. Chem., May 11, 2001; 276(20): 17437 - 17441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D'Addario, P. D. Arora, J. Fan, B. Ganss, R. P. Ellen, and C. A. G. McCulloch Cytoprotection against Mechanical Forces Delivered through beta 1 Integrins Requires Induction of Filamin A J. Biol. Chem., August 17, 2001; 276(34): 31969 - 31977. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
