Fibrin and collagen differentially regulate human dermal microvascular endothelial cell integrins: Stabilization of alpha v/beta 3 mRNA by fibrin

Integrin alpha v beta 3 is specifically but transiently expressed on the ti ps of capillary sprouts as they invade the fibrin clot during angiogenesis of cutaneous wound repair. Specific blocking of alpha v beta 3 function inh ibits granulation tissue formation in cutaneous wounds. The mechanisms of r egulation of alpha v beta 3 expression on human dermal microvascular endoth elial 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 wa s almost undetectable on blood vessels in 7 d wounds rich in collagen, we h ypothesized 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 surfac es coated with collagen, fibronectin, and gelatin, and mRNA levels of integ rin alpha v/beta 3 were determined. Compared with human dermal microvascula r endothelial cells on collagen, mRNA levels of alpha v/beta 3 were higher in human dermal microvascular endothelial cells on fibronectin and on gelat in. To simulate the in vivo environment better, human dermal microvascular endothelial cells cultured on collagen were overlaid fibrin or collagen gel s prior to assessment of alpha v/beta 3 mRNA levels. alpha v/beta 3 mRNA le vels were higher in human dermal microvascular endothelial cells surrounded by a three-dimensional fibrin gel compared with a collagen gel, whether an giogenic 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, al pha 2, and beta 1 mRNA. Three-dimensional fibrin gels enhanced alpha v/beta 3 mRNA stability compared with collagen gels. We propose that the provisio nal matrix molecules in the wound clot regulate angiogenesis associated wit h cutaneous wound repair through their modulation of integrin receptor expr ession.