Association of Latent Transforming Growth Factor-β to Fibroblast Extracellular Matrix: An Insight to Proteolytic Activation

TGF-β1 is the prototype of the so called TGF-β growth factor family. The family consists of an increasing number of different polypeptide modulators of cell growth, differentiation and morphogenesis. Numerous ways to regulate the expression of the TGF-β genes have been identified. Their expression can be affected by autocrine and paracrine mechanisms, and also by some other growth factors. TGF-β:s are also subject to regulation by retinoids, steroid hormones and vitamin D. Active TGF-β regulates transcription, and there is an increasing list of genes that are affected by TGF-β. A characteristic feature in the biology of TGF-β:s is that they are usually secreted from cells in latent forms. TGF-β was originally isolated from the conditioned medium of sarcoma virus transformed cells. The purification involved acidification, which, on the basis of current understanding, activates latent forms. Platelets and placenta are rich sources of TGF-β. We have recently found that TGF-β is not just secreted from cultured cells but is deposited in a latent form to the pericellular space, namely to the extracellular matrix. The latent complex consists of the small latent complex (TGF-β and its propeptide) and a high molecular weight protease resistant binding protein, LTBP (latent TGF-β binding protein). Protease-mediated release from the matrix is supposedly an initial step in the activation of the molecule, which possibly occurs in a coordinate way at the cell surface. The association of latent TGF-β complexes with the pericellular matrices and their release by proteinases implicates that these events participate in a number of biological events where enhanced or focal proteolysis takes place, including cell invasion, tissue remodeling and wound healing.