Proteolytic Release of Latent Transforming Growth Factor-β (TGF-β) Binding Protein-1 (LTBP-1) Fragment in Wound Healing

Transforming growth factor-beta (TGF-beta) is a potent growth factor that contributes to wound healing. TGF-beta is usually secreted in a latent form complexed with its propeptide, latency-associated peptide (LAP), and LAP covalently binds to a molecule of latent TGF-beta binding protein (LTBP). Fibrillin-1 sequesters TGF-beta within connective tissue microfibrils through interaction with LTBP-1. However, it is not clear whether TGF-beta bound to LTBP-1 is available during wound healing. Therefore, we further characterized LTBP-1, the extracellular regulator of TGF-beta in wound healing. LTBP-1 fragments were released from skin by plasmin treatment. The LTBP-1 fragment that is similar to plasmin treatment was also detected in a wound surface. The enzymatic activity of plasmin was also detected in wound surfaces. Immunoblotting analyses showed that the LTBP-1 fragment was preferentially detected in a wound surface with proliferating granulation tissues. These results suggest that proteolytic release of LTBP-1 from a wound surface is physiological and important in regulating wound healing.