Abstract

We investigated the involvement of fibrinolytic system in the process of wound healing as well as angiogenesis in rats using a model system, in which polystyrene capsules with 100 perforated pores filled without (empty capsule) or with fibrin gel (fibrin capsule) were subcutaneously implanted into the dorsal of rats. The intracapsular tissue was accompanied by neovascularization and the tissue weight in the fibrin capsule was three times that of the empty capsule on day 5 after implantation. Both plasminogen activation and amidolytic activities of urokinase-type plasminogen activator (u-PA) in the tissue extracts and intracapsular fluid obtained from the fibrin capsule were higher than those in the empty capsule on day 5 after implantation. Both u-PA and its specific receptor (u-PAR) mRNAs were detected in the intracapsular tissues formed in both capsules. On day 5 after implantation, though the levels of u-PA mRNA in the tissue of the empty capsule and those of the fibrin capsule were not significantly different, more u-PAR mRNA was expressed in the tissue of the fibrin capsule than in the empty capsule. Furthermore, when the cultured endothelial cells were incubated with intracapsular fluids, the proliferation of the cells was significantly enhanced. These results indicate that fibrinolytic activities increase in the presence of fibrin gel, possibly by up-regulation of the u-PA/u-PAR system in the early stage of rat wound healing.

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