Figure 6

Extracellular matrix and TGF-β. Schematic presentation of intracellular TGF-β synthesis, secretion and extracellular immobilization via transglutaminase-dependent fixation of the large latent TGF-β binding protein (LTBP) to extracellular matrix, release by proteases and activation of the latent TGF-β complex by reactive oxygen species (ROS), specific integrins, thrombospondin-1 (TSP-1) or proteases with release of the active TGF-β homodimer, which binds to TGF-β receptors (TβR) III, II, and I to initiate the intracellular signalling cascade of Smad phosphorylation. Regulation of TGF-β occurs at the transcriptional level and, most importantly, by extracellular activation. LAP – latency associated peptide.