| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
From the Departments of Surgery* and Pediatrics, Childrens Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles; the School of Dentistry, University of California Los Angeles, Los Angeles; and the Charles R. Drew University of Medicine and Science, Los Angeles, California
Proteolytic degradation of the provisional fibrin matrix and subsequent substitution by fibroblast-produced collagen are essential features of injury repair. Immunohistochemical studies revealed that although dermal fibroblasts of normal scars and keloids expressed both urokinase type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1), keloid fibroblasts had a much higher PAI-1 expression. In long-term three-dimensional fibrin gel cultures (the in vitro fibroplasia model), normal fibroblasts expressed moderate and modulated activity levels of uPA and PAI-1. In contrast, keloid fibroblasts expressed a persistently high level of PAI-1 and a low level of uPA. The high PAI-1 activity of keloid fibroblasts correlated with their elevated collagen accumulation in fibrin gel cultures. Substituting collagen for fibrin in the gel matrix resulted in increased uPA activity and reduced collagen accumulation of keloid fibroblasts. Furthermore, decreasing PAI-1 activity of keloid fibroblasts in fibrin gel cultures with anti-PAI-1-neutralizing antibodies also resulted in a reduction in collagen accumulation by keloid fibroblasts. Cumulatively, these results suggest that PAI-1 overexpression is a consistent feature of keloid fibroblasts both in vitro and in vivo, and PAI-1 may play a causative role in elevated collagen accumulation of keloid fibroblasts.
This article has been cited by other articles:
 |
|
 |
|
  P. K. Vayalil, M. Olman, J. E. Murphy-Ullrich, E. M. Postlethwait, and R.-M. Liu Glutathione restores collagen degradation in TGF-{beta}-treated fibroblasts by blocking plasminogen activator inhibitor-1 expression and activating plasminogen Am J Physiol Lung Cell Mol Physiol, December 1, 2005; 289(6): L937 - L945. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. de Giorgio-Miller, S. Bottoms, G. Laurent, P. Carmeliet, and S. Herrick Fibrin-Induced Skin Fibrosis in Mice Deficient in Tissue Plasminogen Activator Am. J. Pathol., September 1, 2005; 167(3): 721 - 732. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. H. Chau, C. A. Clavijo, H.-T. Deng, Q. Zhang, K.-J. Kim, Y. Qiu, A. D. Le, and D. K. Ann Etk/Bmx mediates expression of stress-induced adaptive genes VEGF, PAI-1, and iNOS via multiple signaling cascades in different cell systems Am J Physiol Cell Physiol, August 1, 2005; 289(2): C444 - C454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Zhou, R. Song, C. L. Fattman, S. Greenhill, S. Alber, T. D. Oury, A. M.K. Choi, and D. Morse Carbon Monoxide Suppresses Bleomycin-Induced Lung Fibrosis Am. J. Pathol., January 1, 2005; 166(1): 27 - 37. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Torkian, A. T. Yeh, R. Engel, C.-H. Sun, B. J. Tromberg, and B. J. F. Wong Modeling Aberrant Wound Healing Using Tissue-Engineered Skin Constructs and Multiphoton Microscopy Arch Facial Plast Surg, May 1, 2004; 6(3): 180 - 187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wu, Q. Zhang, D. K. Ann, A. Akhondzadeh, H. S. Duong, D. V. Messadi, and A. D. Le Increased vascular endothelial growth factor may account for elevated level of plasminogen activator inhibitor-1 via activating ERK1/2 in keloid fibroblasts Am J Physiol Cell Physiol, April 1, 2004; 286(4): C905 - C912. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
