The Cutaneous Microfibrillar Apparatus Contains Latent Transforming Growth Factor-β Binding Protein-1 (LTBP-1) and is a Repository for Latent TGF-β1

The transforming growth factors-β1 and β2 (TGF-β) stimulate synthesis of extracellular matrix proteins in vitro and appear upregulated in fibrotic conditions, in scar formation, and in wound healing. The extracellular matrix in turn might also act as a scavenger or repository for TGF-β. We therefore studied the in situ distribution of latent TGF binding protein-1 (LTBP-1) and latent TGF-β1 on extracellular matrix elements of normal human skin and skin regenerating from cultured keratinocyte autografts. We localized both LTBP-1 and latent TGF-β1 to fibrillin-containing (elastic) microfibrils. Both LTBP-1 and latent TGF-β1 were already present during the earliest stages of the de novo formation of the microfibrillar apparatus, i.e., on fusiform, randomly oriented microfibrils that later coalesced to form the typical candelabra-like structures in the papillary dermis. We show herewith that LTBP-1 exerts a dual role as a component of fibrillin-microfibrils of the skin and in targeting latent TGF-β1 to the cutaneous microfibrillar apparatus. Thus, this major connective tissue structure does not only serve as a force bearing element and scaffold for elastin deposition in the dermis, but also as an important repository for latent TGF-β in the skin