Potential role for insulin-like growth factor II and vitronectin in the endothelial-mesenchymal transition process.
Endothelial-to-mesenchymal transition (EndoMT) is a process through which certain subsets of endothelial cells lose endothelial characteristics and transform into mesenchymal or smooth muscle-like cells. Emerging evidence suggests that this process plays an important role during vascular development and in many vascular pathologies. As in epithelial-mesenchymal transition, EndoMT seems to progress through a series of important steps whose interdependence and order are not clear, and that some of them are regulated by soluble growth factors. Insulin-like growth factor II (IGFII), apart from being considered important in cancer, angiogenesis, and atherosclerotic lesions, is also considered as essential to embryonic development. Here, we report that addition of IGFII promoted the EndoMT process in the presence of very low amounts of chicken serum to arrested primary embryonic aortic chicken endothelial cells attached to fibronectin (FN), gelatin, or native type I collagen. This was demonstrated by cell spreading, loss of cell-cell contacts, detachment, migration, and transformation. These cellular events also occurred when IGFII was added to medium containing vitronectin (VN). Additionally, we demonstrated that these proteins were present in the spontaneous intimal thickenings that are observed at day 11-13 of chicken embryo development. We also show that alterations in the distribution of VE-cadherin and beta-catenin occur after IGFII and serum or VN stimulation, and propose that the via VN IGFII effects may be facilitated by interaction of the mannose-6-phosphate/IGFII receptor (M6P/IGFIIR) with the urokinase-type plasminogen activator receptor (uPAR) and its ligand (uPA). Collectively, these findings provide the first evidence for a potential role of the IGFII-VN complex during the EndoMT process. From our observations and previous studies, we postulate a working hypothesis supporting a fundamental role for these molecules during EndoMT.
Arciniegas
Enrique
E
Servicio Autónomo Instituto de Biomedicina, Facultad de Medicina, Universidad Central de Venezuela, Apartado de correos 4043, Carmelitas, Caracas 1010, Venezuela. earciniegasbeta@yahoo.com
Neves
Yudith C
YC
Carrillo
Luz M
LM
D000818:Animals; D001011:Aorta / Q000196:embryology / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D002642:Chick Embryo; D024042:Collagen Type I / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology*; D004730:Endothelium, Vascular / Q000196:embryology* / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005780:Gelatin / Q000378:metabolism; D066298:In Vitro Techniques; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism; D008360:Mannosephosphates / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D044967:Serum; D016608:Talin / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D019096:Vitronectin / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D015820:Cadherins; D024042:Collagen Type I; D005353:Fibronectins; D016023:Integrins; D008360:Mannosephosphates; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D016608:Talin; D019096:Vitronectin; D051176:beta Catenin; D007335:Insulin-Like Growth Factor II; D005780:Gelatin; D014568:Urokinase-Type Plasminogen Activator