A alpha and B beta chains of fibrinogen stimulate proliferation of human fibroblasts

During blood coagulation and wound healing, fibrinogen polymerises to form a fibrin matrix, providing a substratum over which connective tissue cells migrate and proliferate. Although a number of growth factors have been implicated in this process, a possible role for the fibrin(ogen) molecules themselves has not been considered. In this study we have investigated the ability of the constituent chains of fibrin(ogen) to induce fibroblast replication. Fibrinogen chains (A alpha 1, A alpha 2, B beta and gamma) were separated by cation exchange chromatography and their mitogenic activity was assessed before and after treatment with thrombin. The A alpha 1, A alpha 2 and B beta chains where all found to stimulate fibroblast replication (23 +/- 2.9%, 29.2 +/- 5.3% and 31.4 +/- 5% stimulation above control, respectively) and on the addition of thrombin this activity was enhanced. No activity was observed in the gamma chain before or after treatment with thrombin. These results indicate that growth promoting activity is inherent in fibrin(ogen) structure, suggesting a novel mechanism for fibroblast proliferation during wound healing.