Endoglin overexpression modulates cellular morphology, migration, and adhesion of mouse fibroblasts.
Endoglin is the gene mutated in hereditary hemorrhagic telangiectasia type 1 (HHT1), a dominantly inherited vascular disorder. Endoglin glycoprotein is a component of the transforming growth factor type beta (TGF-beta) receptor system which is highly expressed by endothelial cells, and at lower levels on fibroblasts and smooth muscle cells, suggesting the involvement of these lineages in the HHT1 vascular dysplasia. Overexpression of endoglin in mouse NCTC929 fibroblasts led to decreased migration in chemotactic and wound healing assays, as well as changes in the cellular morphology. When plated on uncoated surfaces, endoglin transfectants formed intercellular clusters, endoglin being not specifically localized to the cell-cell junctions, but homogenously distributed on the cellular surface. Although the expression of alpha5beta1 integrin and of an activation epitope of beta1 integrin were unchanged, a polyclonal antibody to alpha5beta1 integrin was able to inhibit cluster formation, suggesting the involvement of integrin ligand/s. In fact, coating with fibronectin, laminin, or an RGD-containing 80 kDa fragment of fibronectin were able to prevent the cellular clustering. Furthermore, synthesis of plasminogen activator inhibitor 1 (PAI-1), and to a weak extent that of fibronectin, were inhibited in endoglin transfectants. Thus, the presence of endoglin in mouse NCTC929 fibroblasts is associated with reduced production of certain extracellular matrix (ECM) components, which might explain their altered morphology, migration and intercellular cluster formation.
Guerrero-Esteo
M
M
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid/Spain.
Lastres
P
P
Letamendía
A
A
Pérez-Alvarez
M J
MJ
Langa
C
C
López
L A
LA
Fabra
A
A
García-Pardo
A
A
Vera
S
S
Letarte
M
M
Bernabéu
C
C
D000818:Animals; D015703:Antigens, CD; D002448:Cell Adhesion; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism; D000071063:Endoglin; D005347:Fibroblasts / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007797:Laminin / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011956:Receptors, Cell Surface; D017469:Receptors, Fibronectin / Q000378:metabolism; D014162:Transfection; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism* / Q000502:physiology*; D014945:Wound Healing
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D007797:Laminin; D017395:Plasminogen Activator Inhibitor 1; D011956:Receptors, Cell Surface; D017469:Receptors, Fibronectin; D019010:Vascular Cell Adhesion Molecule-1; D003094:Collagen