Fibrin and collagen differentially regulate human dermal microvascular endothelial cell integrins:: Stabilization of αv/β3 mRNA by fibrin

[摘要] Integrin alpha v beta 3 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 alpha v beta 3 function inhibits granulation tissue formation in cutaneous wounds. The mechanisms of regulation of alpha v beta 3 expression on human dermal microvascular endothelial cells, however, have not been fully delineated. As alpha v beta 3 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 microvascular endothelial cell alpha v beta 3 expression. To address this, human dermal microvascular endothelial cells were cultured on surfaces coated with collagen, fibronectin, and gelatin, and mRNA levels of integrin alpha v/beta 3 were determined. Compared with human dermal microvascular endothelial cells on collagen, mRNA levels of alpha v/beta 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 fibrin or collagen gels prior to assessment of alpha v/beta 3 mRNA levels. alpha v/beta 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. beta 3 mRNA mRNA much faster than alpha v, alpha 2, and beta 1 mRNA. Three-dimensional fibrin gels enhanced alpha v/beta 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.

[发布日期] 1999-12-01

[效力级别]  Proceedings Paper

[关键词] angiogenesis;endothelium;extracellular matrix;integrin;wound healing