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.

Sodium fluoride induces podosome formation in endothelial cells.

Background Information: Fluoride is a well-known G-protein activator. Exposure of cultured cells to its derivatives results in actin cytoskeleton remodelling. Podosomes are actin-based structures endowed with adhesion and matrix-degradation functions.

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.

TGFbeta1-induced aortic endothelial morphogenesis requires signaling by small GTPases Rac1 and RhoA.

TGFbeta is a potent regulator of cell differentiation in many cell types. On aortic endothelial cells, TGFbeta1 displays angiogenic properties in inducing capillary-like tube formation in collagen I gels, in vitro. We investigated cytoskeletal changes that precede tube formation and related these alterations to the effects of TGFbeta1 on the activation state of members of the RhoGTPase family.

Transforming growth factor beta induces rosettes of podosomes in primary aortic endothelial cells.

Cytoskeletal rearrangements are central to endothelial cell physiology and are controlled by soluble factors, matrix proteins, cell-cell interactions, and mechanical forces. We previously reported that aortic endothelial cells can rearrange their cytoskeletons into complex actin-based structures called podosomes when a constitutively active mutant of Cdc42 is expressed. We now report that transforming growth factor beta (TGF-beta) promotes podosome formation in primary aortic endothelial cells.

CD44 and TGFbeta1 synergise to induce expression of a functional NADPH oxidase in promyelocytic cells.

Bone marrow stromal cells produce large amounts of extracellular matrix and cytokines. Amongst them, hyaluronan, a glycosaminoglycan and ligand for the cell surface molecule CD44, and TGFbeta1, a cytokine particularly important in monocyte differentiation. We have studied in vitro the role of hyaluronan and TGFbeta1 in the differentiation process of U937 monocytic progenitor cells.

RhoGTPases and p53 are involved in the morphological appearance and interferon-alpha response of hairy cells.

Hairy cell leukemia is an uncommon B-cell lymphoproliferative disease of unknown etiology in which tumor cells display characteristic microfilamentous membrane projections. Another striking feature of the disease is its exquisite sensitivity to interferon (IFN)-alpha. So far, none of the known IFN-alpha regulatory properties have explained IFN-alpha responsiveness nor have they taken into account the morphological characteristics of hairy cells.