FAK activity is required for HGF to suppress TGF-β1-induced cellular proliferation

Due to the complex nature of the tendon architecture, the regeneration of these tissues results in the formation of scars. As a direct result of scar formation, the ability of the tendon tissues to function is impaired and often results in further damage that has been afflicted to the tendon architecture. The growth and proliferation of tendon fibroblasts involve a complex network of signalling molecules. To understand and aid in the proper repair of this complex tissue network, a more in-depth understanding is required in the events that induce the growth of tendon cells. Several studies have shown the apoptotic mechanisms induced by the mitogen, hepatocyte growth factor, in multiple biological and pathological systems. In our recent research, we have described a mechanism where hepatocyte growth factor (HGF) is able to inhibit the proliferative effects of transforming growth factor-β1 (TGF-β1) and induce apoptosis in rat tendon fibroblasts. Transforming growth factor-β1 is able to induce the proliferation of fibroblast cells by increasing both the gene expression and protein levels of α-smooth muscle actin (α-SMA) and c-MET. We have also shown that inhibition of extracellular signal-regulated kinase 1/2 does not block hepatocyte growth factor-induced growth arrest. However, we have shown that blocking the activity of focal adhesion kinase can prevent the growth inhibition ability of hepatocyte growth factor in tendon fibroblasts. Collectively, our studies show growth inhibitory pathway in tendon fibroblasts induced by hepatocyte growth factor and mediated focal adhesion kinase.