TGFβ-induced endothelial podosomes mediate basement membrane collagen degradation in arterial vessels

Podosomes are specialized plasma-membrane actin-based microdomains that combine adhesive and proteolytic activities to spatially restrict sites of matrix degradation in in vitro assays, but the physiological relevance of these observations remain unknown. Inducible rings of podosomes (podosome rosettes) form in cultured aortic cells exposed to the inflammatory cytokine TGF beta. In an attempt to prove the existence of podosomes in living tissues, we developed an ex vivo endothelium observation model. This system enabled us to visualize podosome rosettes in the endothelium of native arterial vessel exposed to biologically active TGF beta. Podosomes induced in the vessel appear similar to those formed in cultured cells in terms of molecular composition, but in contrast to the latter, arrange in a protruding structure that is similar to invadopodia. Local degradation of the basement membrane scaffold protein collagen-IV, is observed underneath the structures. Our results reveal for the first time the presence of podosome rosettes in the native endothelium and provide evidence for their capacity to degrade the basement membrane, opening up new avenues to study their role in vascular pathophysiology. We propose that podosome rosettes are involved in arterial vessel remodeling.