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J.Health Sci., 55(3), 468-472, 2009

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

Koji Mizuno,a Hiroshi Wachi,*, a Zenzo Isogai,b Masahiko Yoneda,c Satoshi Fujii,d Ken Watanabe,e and Yoshiyuki Seyamaa

aDepartment of Clinical Chemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan, bDepartment of Advanced Medicine, National Center for Geriatrics and Gerontology, 36-3 Gengo, Moriokacho, Obu, Aichi, 474-8522 Japan, cAichi Prefectural College of Nursing and Health, Tougoku, kamishidami, Moriyama-ku, Nagoya 463-8502, Japan, dDepartment of Molecular and Cellular Pathobiology and Therapeutics, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-Dori, Mizuho-ku Nagoya, 467-8603 Japan and eDepartment of Bone and Joint Disease, National Center for Geriatrics and Gerontology, 36-3 Gengo, Morioka-cho, Obu, Aichi 474-8522, Japan

Transforming growth factor-β (TGF-β) is a potent growth factor that contributes to wound healing. TGF-β 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-β binding protein (LTBP). Fibrillin-1 sequesters TGF-β within connective tissue microfibrils through interaction with LTBP-1. However, it is not clear whether TGF-β bound to LTBP-1 is available during wound healing. Therefore, we further characterized LTBP-1, the extracellular regulator of TGF-β 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.