1. ^*Department of Dermatology, Medicine, School of Medicine, State University of New York at Stony Brook, Stony Brook, New York, U.S.A.
2. ^†Department of Pathology and School of Medicine, State University of New York at Stony Brook, Stony Brook, New York, U.S.A.
3. ^‡Department of Medicine, School of Medicine, State University of New York at Stony Brook, Stony Brook, New York, U.S.A.
4. ^§Dermatology Section, Medicine Service, VAMC, Northport, New York, U.S.A.

Correspondence: Dr Marcia G. Tonnesen, Department of Dermatology, Health Sciences Center T16060-Z8165, State University of New York at Stony Brook, Stony Brook, NY 11794-8165

¹This paper was presented in part at the Society for Investigative Dermatology meeting in Washington, DC in May 1997; at the Wound Healing Society meeting in Nashville, TN in June 1997; and at the International Investigative Dermatology meeting in Cologne, Germany in May 1998.

Received 1 March 1999; Revised 13 July 1999; Accepted 26 August 1999.

Abstract

Integrin v3 is specifically but transiently expressed on the tips of capillary sprouts as they invade the fibrin clot during angiogenesis of cutaneous wound repair. Specific blocking of v3 function inhibits granulation tissue formation in cutaneous wounds. The mechanisms of regulation of v3 expression on human dermal microvascular endothelial cells, however, have not been fully delineated. As v3 was highly expressed on capillary sprouts in 5 d wounds rich in fibrin, but was almost undetectable on blood vessels in 7 d wounds rich in collagen, we hypothesized that the extracellular matrix environment could regulate human dermal micro- vascular endothelial cell v3 expression. To address this, human dermal microvascular endothelial cells were cultured on surfaces coated with collagen, fibronectin, and gelatin, and mRNA levels of integrin v/3 were determined. Compared with human dermal microvascular endothelial cells on collagen, mRNA levels of v/3 were higher in human dermal microvascular endothelial cells on fibronectin and on gelatin. To simulate the in vivo environment better, human dermal microvascular endothelial cells cultured on collagen were overlaid by fibrin or collagen gels prior to assessment of v/3 mRNA levels. v/3 mRNA levels were higher in human dermal microvascular endothelial cells surrounded by a three-dimensional fibrin gel compared with a collagen gel, whether angiogenic factors were present or absent. As modulation of mRNA stability is a potential regulatory mechanism for integrin expression, integrin subunit mRNA stability was assessed. 3 mRNA decayed much faster than v, 2, and 1 mRNA. Three-dimensional fibrin gels enhanced v/3 mRNA stability compared with collagen gels. We propose that the provisional matrix molecules in the wound clot regulate angiogenesis associated with cutaneous wound repair through their modulation of integrin receptor expression.