| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
From the Laboratory of Cell Regulation and Carcinogenesis* and the Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland; and the Department of Obstetrics/Gynecology, Institute of Wound Healing, University of Florida, Gainesville, Florida
Transforming growth factor (TGF)-ß regulates many aspects of wound repair including inflammation, chemotaxis, and deposition of extracellular matrix. We previously showed that epithelialization of incisional wounds is accelerated in mice null for Smad3, a key cytoplasmic mediator of TGF-ß signaling. Here, we investigated the effects of loss of Smad3 on healing of wounds in skin previously exposed to ionizing radiation, in which scarring fibrosis complicates healing. Cutaneous wounds made in Smad3-null mice 6 weeks after irradiation showed decreased wound widths, enhanced epithelialization, and reduced numbers of neutrophils and myofibroblasts compared to wounds in irradiated wild-type littermates. Differences in breaking strength of wild-type and Smad3-null wounds were not significant. As shown previously for neutrophils, chemotaxis of primary dermal fibroblasts to TGF-ß required Smad3, but differentiation of fibroblasts to myofibroblasts by TGF-ß was independent of Smad3. Previous irradiation-enhanced induction of connective tissue growth factor mRNA in wild-type, but not Smad3-null fibroblasts, suggested that this may contribute to the heightened scarring in irradiated wild-type skin as demonstrated by Picrosirius red staining. Overall, the data suggest that attenuation of Smad3 signaling might improve the healing of wounds in previously irradiated skin commensurate with an inhibition of fibrosis.
This article has been cited by other articles:
 |
|
 |
|
  A. Masszi, P. Speight, E. Charbonney, M. Lodyga, H. Nakano, K. Szaszi, and A. Kapus Fate-determining mechanisms in epithelial-myofibroblast transition: major inhibitory role for Smad3 J. Cell Biol., February 8, 2010; 188(3): 383 - 399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Martinez-Ferrer, A.-R. Afshar-Sherif, C. Uwamariya, B. de Crombrugghe, J. M. Davidson, and N. A. Bhowmick Dermal Transforming Growth Factor-{beta} Responsiveness Mediates Wound Contraction and Epithelial Closure Am. J. Pathol., January 1, 2010; 176(1): 98 - 107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Maxhimer, D. R. Soto-Pantoja, L. A. Ridnour, H. B. Shih, W. G. DeGraff, M. Tsokos, D. A. Wink, J. S. Isenberg, and D. D. Roberts Radioprotection in Normal Tissue and Delayed Tumor Growth by Blockade of CD47 Signaling Science Translational Medicine, October 21, 2009; 1(3): 3ra7 - 3ra7. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Wu, D. S. Melichian, M. de la Garza, K. Gruner, S. Bhattacharyya, L. Barr, A. Nair, S. Shahrara, P. H.S. Sporn, T. A. Mustoe, et al. Essential Roles for Early Growth Response Transcription Factor Egr-1 in Tissue Fibrosis and Wound Healing Am. J. Pathol., September 1, 2009; 175(3): 1041 - 1055. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Webber, S. Meran, R. Steadman, and A. Phillips Hyaluronan Orchestrates Transforming Growth Factor-{beta}1-dependent Maintenance of Myofibroblast Phenotype J. Biol. Chem., April 3, 2009; 284(14): 9083 - 9092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. GREENBERGER Radioprotection In Vivo, March 1, 2009; 23(2): 323 - 336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. W. Clavin, T. Avraham, J. Fernandez, S. V. Daluvoy, M. A. Soares, A. Chaudhry, and B. J. Mehrara TGF-{beta}1 is a negative regulator of lymphatic regeneration during wound repair Am J Physiol Heart Circ Physiol, November 1, 2008; 295(5): H2113 - H2127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Isenberg, J. B. Maxhimer, F. Hyodo, M. L. Pendrak, L. A. Ridnour, W. G. DeGraff, M. Tsokos, D. A. Wink, and D. D. Roberts Thrombospondin-1 and CD47 Limit Cell and Tissue Survival of Radiation Injury Am. J. Pathol., October 1, 2008; 173(4): 1100 - 1112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. C. Flanders, B. M. Ho, P. R. Arany, C. Stuelten, M. Mamura, M. O. Paterniti, A. Sowers, J. B. Mitchell, and A. B. Roberts Absence of Smad3 Induces Neutrophil Migration after Cutaneous Irradiation: Possible Contribution to Subsequent Radioprotection Am. J. Pathol., July 1, 2008; 173(1): 68 - 76. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V Haydont, C Bourgier, and M-C Vozenin-Brotons Rho/ROCK pathway as a molecular target for modulation of intestinal radiation-induced toxicity Br. J. Radiol., September 1, 2007; 80(Special_Issue_1): S32 - S40. [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]
|
|
|
|
 |
|
 S. Saika, K. Ikeda, O. Yamanaka, K. C. Flanders, Y. Ohnishi, Y. Nakajima, Y. Muragaki, and A. Ooshima Adenoviral gene transfer of BMP-7, Id2, or Id3 suppresses injury-induced epithelial-to-mesenchymal transition of lens epithelium in mice Am J Physiol Cell Physiol, January 1, 2006; 290(1): C282 - C289. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Finotto, M. Hausding, A. Doganci, J. H. Maxeiner, H. A. Lehr, C. Luft, P. R. Galle, and L. H. Glimcher Asthmatic changes in mice lacking T-bet are mediated by IL-13 Int. Immunol., August 1, 2005; 17(8): 993 - 1007. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kopp, E. Preis, H. Said, B. Hafemann, L. Wickert, A. M. Gressner, N. Pallua, and S. Dooley|| Abrogation of Transforming Growth Factor-{beta} Signaling by SMAD7 Inhibits Collagen Gel Contraction of Human Dermal Fibroblasts J. Biol. Chem., June 3, 2005; 280(22): 21570 - 21576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. McClung, K. A. Mehl, R. W. Thompson, L. L. Lowe, and J. A. Carson Nandrolone decanoate modulates cell cycle regulation in functionally overloaded rat soleus muscle Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2005; 288(6): R1543 - R1552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Saika, K. Ikeda, O. Yamanaka, T. Miyamoto, Y. Ohnishi, M. Sato, Y. Muragaki, A. Ooshima, Y. Nakajima, W. W.-Y. Kao, et al. Expression of Smad7 in Mouse Eyes Accelerates Healing of Corneal Tissue after Exposure to Alkali Am. J. Pathol., May 1, 2005; 166(5): 1405 - 1418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V Meineke The role of damage to the cutaneous system in radiation-induced multi-organ failure Br. J. Radiol., January 1, 2005; Supplement_27(1): 95 - 99. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M H Barcellos-Hoff How tissues respond to damage at the cellular level: orchestration by transforming growth factor-{beta} (TGF-{beta}) Br. J. Radiol., January 1, 2005; Supplement_27(1): 123 - 127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Lakos, S. Takagawa, S.-J. Chen, A. M. Ferreira, G. Han, K. Masuda, X.-J. Wang, L. A. DiPietro, and J. Varga Targeted Disruption of TGF-{beta}/Smad3 Signaling Modulates Skin Fibrosis in a Mouse Model of Scleroderma Am. J. Pathol., July 1, 2004; 165(1): 203 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Xavier, E. Piek, M. Fujii, D. Javelaud, A. Mauviel, K. C. Flanders, A. M. Samuni, A. Felici, M. Reiss, S. Yarkoni, et al. Amelioration of Radiation-induced Fibrosis: INHIBITION OF TRANSFORMING GROWTH FACTOR-{beta} SIGNALING BY HALOFUGINONE J. Biol. Chem., April 9, 2004; 279(15): 15167 - 15176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Saika, S. Kono-Saika, Y. Ohnishi, M. Sato, Y. Muragaki, A. Ooshima, K. C. Flanders, J. Yoo, M. Anzano, C.-Y. Liu, et al. Smad3 Signaling Is Required for Epithelial-Mesenchymal Transition of Lens Epithelium after Injury Am. J. Pathol., February 1, 2004; 164(2): 651 - 663. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
