ALK5 and ALK1 play antagonistic roles in transforming growth factor β-induced podosome formation in aortic endothelial cells.

Transforming growth factor β (TGF-β) and related cytokines play a central role in the vascular system. In vitro, TGF-β induces aortic endothelial cells to assemble subcellular actin-rich structures specialized for matrix degradation called podosomes. To explore further this TGF-β-specific response and determine in which context podosomes form, ALK5 and ALK1 TGF-β receptor signaling pathways were investigated in bovine aortic endothelial cells.

Zona occludens proteins modulate podosome formation and function.

Podosomes are highly dynamic structures that are involved in cell adhesion and extracellular matrix remodeling. They present as intracellular columns composed of an actin-rich core region and a surrounding ring-like structure containing focal adhesion proteins, actin binders as well as cell signaling molecules. A key player in podosome biogenesis is the scaffolding protein cortactin, which is thought to control actin assembly at the core region.

TGFbeta-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 TGFbeta. In an attempt to prove the existence of podosomes in living tissues, we developed an ex vivo endothelium observation model.

Regulatory signals for endothelial podosome formation.

Podosomes are punctate actin-rich adhesion structures which spontaneously form in cells of the myelomonocytic lineage. Their formation is dependent on Src and RhoGTPases. Recently, podosomes have also been described in vascular cells.

TGFbeta1 regulates endothelial cell spreading and hypertrophy through a Rac-p38-mediated pathway.

Background Information: TGFbeta (transforming growth factor beta) is a multifunctional cytokine and a potent regulator of cell growth, migration and differentiation in many cell types. In the vascular system, TGFbeta plays crucial roles in vascular remodelling, but the signalling pathways involved remain poorly characterized.

Results: Using the model of porcine aortic endothelial cells, we demonstrated that TGFbeta stimulates cellular spreading when cells are on collagen I.