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Diabetes 54:2143-2154, 2005
© 2005 by the American Diabetes Association, Inc.

Tissue Factor as a Link Between Wounding and Tissue Repair

Jiang Chen1,2, Michael Kasper3, Tobias Heck1, Katsumi Nakagawa1,4, Per M. Humpert1, Ling Bai1,5, Gang Wu1,5, Youming Zhang1, Thomas Luther3, Martin Andrassy1, Stephan Schiekofer1, Andreas Hamann1, Michael Morcos1, Baoshen Chen5, David M. Stern6, Peter P. Nawroth1, and Angelika Bierhaus1

1 Department of Medicine I, University of Heidelberg, Heidelberg, Germany
2 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas
3 Institutes of Anatomy and Pathology, Technical University of Dresden, Dresden, Germany
4 Medical Service Center Toji-in Kitamachi, Ritsumeikan University, Kita-ku, Kyoto, Japan
5 Department of Biochemistry, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
6 Dean’s Office, Medical College of Georgia, Augusta, Georgia

The initial phase of wound repair involves inflammation, induction of tissue factor (TF), formation of a fibrin matrix, and growth of new smooth muscle actin ({alpha}-SMA)-positive vessels. In diabetes, TF induction in response to cutaneous wounding, which ordinarily precedes increased expression of vascular endothelial growth factor (VEGF) and {alpha}-SMA transcription, is diminished, though not to a degree causing excessive local bleeding. Enhanced TF expression in wounds of diabetic mice caused by somatic TF gene transfer increased VEGF transcription and translation and, subsequently, enhanced formation of new blood vessels and elevated blood flow. Furthermore, increased levels of TF in wounds of diabetic mice enhanced wound healing; the time to achieve 50% wound closure was reduced from 5.5 days in untreated diabetic mice to 4.1 days in animals undergoing TF gene transfer (this was not statistically different from wound closure in nondiabetic mice). Thus, cutaneous wounds in diabetic mice display a relative deficiency of TF compared with nondiabetic controls, and this contributes to delayed wound repair. These data establish TF expression as an important link between the early inflammatory response to cutaneous wounding and reparative processes.


Address correspondence and reprint requests to Angelika Bierhaus, PhD, University of Heidelberg, Department of Medicine I, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. E-mail: angelika_bierhaus{at}med.uni-heidelberg.de

Abbreviations: {alpha}-SMA, {alpha}-smooth muscle actin; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; NF-{kappa}B, nuclear factor-{kappa}B; TF, tissue factor; VEGF, vascular endothelial growth factor


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[Abstract] [Full Text] [PDF]




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Copyright © 2005 by the American Diabetes Association.