Tissue Factor as a Link Between Wounding and Tissue Repair

• Published in: Diabetes (New York, N.Y.) Vol. 54; no. 7; pp. 2143 - 2154
• Main Authors: JIANG CHEN, KASPER, Michael, SCHIEKOFER, Stephan, HAMANN, Andreas, MORCOS, Michael, BAOSHEN CHEN, STERN, David M, NAWROTH, Peter P, BIERHAUS, Angelika, HECK, Tobias, NAKAGAWA, Katsumi, HUMPERT, Per M, LING BAI, GANG WU, YOUMING ZHANG, LUTHER, Thomas, ANDRASSY, Martin
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.07.2005
• Subjects: Angiogenesis; Animals; Biological and medical sciences; Care and treatment; Cytokines; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - physiopathology; Diabetes. Impaired glucose tolerance; DNA Primers; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Experiments; Glucose; Inflammation; Kinases; Medical sciences; Mice; Mice, Inbred NOD; Observations; Polymerase Chain Reaction; Signal transduction; Skin; Skin - injuries; Smooth muscle; Thromboplastin - genetics; Thromboplastin - physiology; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Wound healing; Wound Healing - genetics; Wound Healing - physiology; Wounds and Injuries - genetics; Wounds and Injuries - physiopathology; Germany; Denmark; Endocrinopathy; Repair; Wound; Diabetes mellitus; Tissue factor
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.54.7.2143

Tissue Factor as a Link Between Wounding and Tissue Repair Jiang Chen 1 2 , Michael Kasper 3 , Tobias Heck 1 , Katsumi Nakagawa 1 4 , Per M. Humpert 1 , Ling Bai 1 5 , Gang Wu 1 5 , Youming Zhang 1 , Thomas Luther 3 , Martin Andrassy 1 , Stephan Schiekofer 1 , Andreas Hamann 1 , Michael Morcos 1 , Baoshen Chen 5 , David M. Stern 6 , Peter P. Nawroth 1 and Angelika Bierhaus 1 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 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 Abstract 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 (α-SMA)-positive vessels. In diabetes, TF induction in response to cutaneous wounding, which ordinarily precedes increased expression of vascular endothelial growth factor (VEGF) and α-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. α-SMA, α-smooth muscle actin GAPDH, glyceraldehyde-3-phosphate dehydrogenase NF-κB, nuclear factor-κB TF, tissue factor VEGF, vascular endothelial growth factor Footnotes Accepted March 24, 2005. Received July 12, 2003. DIABETES