The αvβ3
integrin, an endothelial cells' receptor-binding
fibronectin (FN) in the extracellular matrix (ECM) of blood vessels, regulates ECM remodeling during migration, invasion, angiogenesis, wound healing and
inflammation, and is also involved in the epithelial mesenchymal transition. In vitro-grown human control fibroblasts organize a fibrillar network of FN, which is preferentially bound on the entire cell surface to its canonical α5β1
integrin receptor, whereas the αvβ3
integrin is present only in rare patches in focal contacts. We report on the preferential recruitment of the αvβ3
integrin, due to the lack of FN-ECM and its canonical
integrin receptor, in dermal fibroblasts from Ehlers-Danlos syndromes (EDS) and arterial tortuosity syndrome (ATS), which are rare multisystem connective tissue disorders. We review our previous findings that unraveled different biological mechanisms elicited by the αvβ3
integrin in fibroblasts derived from patients affected with classical (cEDS), vascular (vEDS), hypermobile EDS (hEDS), hypermobility spectrum disorders (HSD), and ATS. In cEDS and vEDS, respectively, due to defective type V and type III
collagens, αvβ3 rescues patients' fibroblasts from anoikis through a paxillin-p60Src-mediated cross-talk with the
EGF receptor. In hEDS and HSD, without a defined molecular basis, the αvβ3
integrin transduces to the ILK-Snail1-axis inducing a fibroblast-to-myofibroblast-transition. In ATS cells, the deficiency of the
dehydroascorbic acid transporter GLUT10 leads to redox imbalance, ECM disarray together with the activation of a non-canonical αvβ3
integrin-TGFBRII signaling, involving p125FAK/p60Src/p38MAPK. The characterization of these different biological functions triggered by αvβ3 provides insights into the multifaced nature of this
integrin, at least in cultured dermal fibroblasts, offering future perspectives for research in this field.