Endoglin overexpression modulates cellular morphology, migration, and adhesion of mouse fibroblasts

Endoglin is the gene mutated in hereditary hemorrhagic telangiectasia type 1 (HRM), a dominantly inherited vascular disorder. Endoglin glycoprotein is a component of the transforming growth factor type beta (TGF-beta) recepto r system which is highly expressed by endothelial cells, and at lower level s on fibroblasts and smooth muscle cells, suggesting the involvement of the se lineages in the HHT1 vascular dysplasia, Overexpression of endoglin in m ouse NCTC929 fibroblasts led to decreased migration in chemotactic and woun d healing assays, as well as changes in the cellular morphology. When plate d on uncoated surfaces, endoglin transfectants formed intercellular cluster s, endoglin being not specifically localized to the cell-cell junctions, bu t homogenously distributed on the cellular surface. Although the expression of alpha 5 beta 1 integrin and of an activation epitope of beta 1 integrin were unchanged, a polyclonal antibody to alpha 5 beta 1 integrin was able to inhibit cluster formation, suggesting the involvement of integrin ligand /s. In fact, coating,vith fibronectin, laminin, or an RGD-containing 80 kDa fragment of fibronectin were able to prevent the cellular clustering. Furt hermore, synthesis of plasminogen activator inhibitor 1 (PAI-1), and to a w eak extent that of fibronectin, were inhibited in endoglin transfectants, T hus, the presence of endoglin in mouse NCTC929 fibroblasts is associated wi th reduced production of certain extracellular matrix (ECM) components, whi ch might explain their altered morphology, migration and intercellular clus ter formation.