TGF-ß Signaling (platelets and monocytes)
Platelet hyper-reactivity in conditions like diabetes predisposes to an enhanced incidence of thrombosis. Researchers at the IVS study the role of Ca2+-activated proteases (calpains) in the limited proteolysis of platelet proteins, which affects protein function. Platelet constituents (RANTES, microRNAs and activated calpain) can also be transferred to the vascular wall to affect the function of endothelial cells and even initiate the sterile inflammation that underlies endothelial dysfunction. Platelet-derived transforming growth factor (TGF)-ß can also contribute to endothelial to mesenchymal transformation and we are assessing the role of secreted modular calcium binding protein 1 (SMOC1) in this process. To date we have linked SMOC-1 with altered ALK-5 signalling, angiogenesis and thrombin activity as well endothelial cell barrier function.
