Keratinocyte-specific expression of human thrombomodulin in transgenic mice: effects on epidermal differentiation and cutaneous wound healing.

Abstract Thrombomodulin is a cell-surface glycoprotein that regulates coagulation and fibrinolysis. Expression of thrombomodulin by epidermal keratinocytes is tightly regulated during squamous differentiation and cutaneous wound healing. To determine the consequences of overexpression of thrombomodulin on squamous differentiation and wound healing in vivo, we expressed full-length human thrombomodulin in transgenic mice using the human keratin 14 promoter. Human thrombomodulin was detected in keratinocytes of transgenic mice by immunohistochemistry and protein C activation assays. Full-thickness cutaneous wounds were created on the dorsum of transgenic mice and nontransgenic littermates, and allowed to heal for up to 35 days. Transgenic mice had normal viability and appeared healthy up to one year of age. In the skin, human thrombomodulin was expressed in basal and suprabasal keratinocytes, with variable expression in the outer root sheath of hair follicles. Thrombomodulin activity in neonatal epidermis was 2.5- to 3-fold higher in transgenic mice than in nontransgenic littermates (p