This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Peterson, J. J. Articles by Lentz, S. R. Search for Related Content PubMed PubMed Citation Articles by Peterson, J. J. Articles by Lentz, S. R.

(American Journal of Pathology. 1999;155:1569-1575.)
© 1999 American Society for Investigative Pathology

Regular Articles

Expression of Thrombomodulin and Consequences of Thrombomodulin Deficiency during Healing of Cutaneous Wounds

Jeffrey J. Peterson^*, Helen B. Rayburn, Donna J. Lager, Thomas J. Raife^§, G. Patrick Kealey^¶, Robert D. Rosenberg^* and Steven R. Lentz^||

From the Veterans Affairs Medical Center,||
Iowa City, Iowa; the Departments of Pathology,^*
Surgery,^¶
and Internal Medicine,||
University of Iowa College of Medicine, Iowa City, Iowa; the Department of Biology,
Massachusetts Institute of Technology, Cambridge, Massachusetts; the Department of Laboratory Medicine and Pathology,
Mayo Clinic, Rochester, Minnesota; and the Blood Center of Southeastern Wisconsin,^§
Milwaukee, Wisconsin

Thrombomodulin is a cell surface anticoagulant that is expressed by endothelial cells and epidermal keratinocytes. Using immunohistochemistry, we examined thrombomodulin expression during healing of partial-thickness wounds in human skin and full-thickness wounds in mouse skin. We also examined thrombomodulin expression and wound healing in heterozygous thrombomodulin-deficient mice, compound heterozygous mice that have <1% of normal thrombomodulin anticoagulant activity, and chimeric mice derived from homozygous thrombomodulin-deficient embryonic stem cells. In both human and murine wounds, thrombomodulin was absent in keratinocytes at the leading edge of the neoepidermis, but it was expressed strongly by stratifying keratinocytes within the neoepidermis. No differences in rate or extent of reepithelialization were observed between wild-type and thrombomodulin-deficient mice. In chimeric mice, both thrombomodulin-positive and thrombomodulin-negative keratinocytes were detected within the neoepidermis. Compared with wild-type mice, heterozygous and compound heterozygous thrombomodulin-deficient mice exhibited foci of increased collagen deposition in the wound matrix. These findings demonstrate that expression of thrombomodulin in keratinocytes is regulated during cutaneous wound healing. Severe deficiency of thrombomodulin anticoagulant activity does not appear to alter reepithelialization but may influence collagen production by fibroblasts in the wound matrix.

This article has been cited by other articles:

				S. Roy, S. Khanna, C. Rink, S. Biswas, and C. K. Sen Characterization of the acute temporal changes in excisional murine cutaneous wound inflammation by screening of the wound-edge transcriptome Physiol Genomics, July 9, 2008; 34(2): 162 - 184. [Abstract] [Full Text] [PDF]

				R. G. Bagley, J. Walter-Yohrling, X. Cao, W. Weber, B. Simons, B. P. Cook, S. D. Chartrand, C. Wang, S. L. Madden, and B. A. Teicher Endothelial Precursor Cells As a Model of Tumor Endothelium: Characterization and Comparison with Mature Endothelial Cells Cancer Res., September 15, 2003; 63(18): 5866 - 5873. [Abstract] [Full Text] [PDF]

				W. W. Piette, S. R. Lentz, N. Kao, J. A. Hazelzet, E. D. de Kleijn, R. de Groot, S. N. Faust, R. S. Heyderman, and M. Levin Endothelial Protein C Activation in Meningococcal Sepsis N. Engl. J. Med., December 13, 2001; 345(24): 1776 - 1777. [Full Text] [PDF]