TGF-β IS RELEASED BY DISSOCIATION OF LATENT TGF-β BINDING PROTEIN-1 (LTBP-1) FROM CUTANEOUS MICROFIBRILS

概要

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TGF-βis a potent growth factor that enhances production of extracellular matrix (ECM). TGF-βis involved in wound healing and fibrosis. Cutaneous microfibrils are mainly composed of fibrillin and an extracellular element with elasticity. Recently, latent transforming growth factor-β binding protein-1 (LTBP-1) has been found to interact with fibrillin and localize to microfibrils. Therefore, cutaneous microfibrils target TGF-β within dermal connective tissues via LTBP-1. However, mechanism how TGF-β is released from cutaneous microfibrils is unknown. Expression of both spliced and non-spliced forms of LTBP-1 by dermal fibroblasts was shown. Extraction studies using guanidine hydrochloride suggested non-covalent interaction between microfibrils and LTBP-1. Other extraction studies utilizing plasmin treatment revealed the presence of cross-linked LTBP-1 in aged skin. Immunohistochemical analysis after plasmin treatment also showed decreased staining of LTBP-1 in a concentration of plasmin dependent manner, suggesting that plasmin released LTBP-1 from cutaneous microfibrils. Western blot analysis of the treated solution showed consistent amount of release of LTBP-1 from dermal matrix. These results indicate that cutaneous microfibrils regulate TGF-βactivity through proteolytic release of LTBP-1.
名古屋市立大学の論文
2003-02-28