| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
From the Department of Oral Biological and Medical Sciences,* Laboratory of Periodontal Biology, Faculty of Dentistry, University of British Columbia, Vancouver, Canada; Research Pathology Department, Biogen, Inc. Cambridge, Massachusetts; the Department of Dermatology and Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland; Genomic Pharmacology, Millenium Pharmaceuticals, Cambridge, Massachusetts; Viikki Transgenic Unit,|| University of Helsinki, Helsinki, Finland, the Department of Surgery,** Turku University Central Hospital, Turku, Finland; and the Department of Biology, University of Jyväskylä, Jyväskylä, Finland
Integrin 
vß6 is an epithelial cell-specific receptor that is not normally expressed by resting epithelium but its expression is induced during wound healing. The function of vß6-integrin in wound repair is not clear. In the present study, we showed that ß6-integrin expression was strongly up-regulated in the epidermis in human chronic wounds but not in different forms of skin fibrosis. To test whether increased ß6-integrin expression plays a role in abnormal wound healing we developed four homozygous transgenic mouse lines that constitutively expressed human ß6-integrin in the epithelium. The mice developed normally and did not show any histological abnormalities in the skin. The rate of experimental skin wound closure was unaltered and the wounds healed without significant scar formation. However, during breeding program 16.1 to 27.0% of transgenic mice developed spontaneous, progressing fibrotic chronic ulcers. None of the wild-type animals developed these lesions. The chronic lesions had areas with severe fibrosis and numerous activated macrophages and fibroblasts expressing transforming growth factor (TGF)-ß. The level of TGF-ß1 was significantly increased in the lesions as compared with normal skin. The findings suggest that increased vß6-integrin in keratinocytes plays an active part in abnormal wound healing possibly through a mechanism involving increased activation of TGF-ß.
This article has been cited by other articles:
 |
|
 |
|
  T. Tabata, H. Kawakatsu, E. Maidji, T. Sakai, K. Sakai, J. Fang-Hoover, M. Aiba, D. Sheppard, and L. Pereira Induction of an Epithelial Integrin {alpha}v{beta}6 in Human Cytomegalovirus-Infected Endothelial Cells Leads to Activation of Transforming Growth Factor-{beta}1 and Increased Collagen Production Am. J. Pathol., April 1, 2008; 172(4): 1127 - 1140. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Santulli, W. A. Kinney, S. Ghosh, B. L. DeCorte, L. Liu, R. W. A. Tuman, Z. Zhou, N. Huebert, S. E. Bursell, A. C. Clermont, et al. Studies with an Orally Bioavailable {alpha}V Integrin Antagonist in Animal Models of Ocular Vasculopathy: Retinal Neovascularization in Mice and Retinal Vascular Permeability in Diabetic Rats J. Pharmacol. Exp. Ther., March 1, 2008; 324(3): 894 - 901. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. S. Horan, S. Wood, V. Ona, D. J. Li, M. E. Lukashev, P. H. Weinreb, K. J. Simon, K. Hahm, N. E. Allaire, N. J. Rinaldi, et al. Partial Inhibition of Integrin {alpha}v 6 Prevents Pulmonary Fibrosis without Exacerbating Inflammation Am. J. Respir. Crit. Care Med., January 1, 2008; 177(1): 56 - 65. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Agren and M. Werthen The Extracellular Matrix in Wound Healing: A Closer Look at Therapeutics for Chronic Wounds International Journal of Lower Extremity Wounds, June 1, 2007; 6(2): 82 - 97. [Abstract] [PDF]
|
|
|
|
 |
|
 D. DiCara, C. Rapisarda, J. L. Sutcliffe, S. M. Violette, P. H. Weinreb, I. R. Hart, M. J. Howard, and J. F. Marshall Structure-Function Analysis of Arg-Gly-Asp Helix Motifs in {alpha}vbeta6 Integrin Ligands J. Biol. Chem., March 30, 2007; 282(13): 9657 - 9665. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Hakkinen and A. Csiszar Hereditary Gingival Fibromatosis: Characteristics and Novel Putative Pathogenic Mechanisms J. Dent. Res., January 1, 2007; 86(1): 25 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hahm, M. E. Lukashev, Y. Luo, W. J. Yang, B. M. Dolinski, P. H. Weinreb, K. J. Simon, L. Chun Wang, D. R. Leone, R. R. Lobb, et al. {alpha}v{beta}6 Integrin Regulates Renal Fibrosis and Inflammation in Alport Mouse Am. J. Pathol., January 1, 2007; 170(1): 110 - 125. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
