Microfibrils and fibrillin-1 induce integrin-mediated signaling, proliferation and migration in human endothelial cells. - DyCTim : Dynamique Cellulaire / Tissulaire et Microscopie fonctionnelle Accéder directement au contenu
Article Dans Une Revue American Journal of Physiology - Cell Physiology Année : 2010

Microfibrils and fibrillin-1 induce integrin-mediated signaling, proliferation and migration in human endothelial cells.

Résumé

Microfibrils are macromolecular complexes associated with elastin to form elastic fibers that endow extensible tissues, such as arteries, lungs, and skin, with elasticity property. Fibrillin-1, the main component of microfibrils, is a 350-kDa glycoprotein for which genetic haploinsufficiency in humans can lead to Marfan syndrome, a severe polyfeatured pathology including aortic aneurysms and dissections. Microfibrils and fibrillin-1 fragments mediate adhesion of several cell types, including endothelial cells, while fibrillin-1 additionally triggers lung and mesangial cell migration. However, fibrillin-1-induced intracellular signaling is unknown. We have studied the signaling events induced in human umbilical venous endothelial cells (HUVECs) by aortic microfibrils as well as recombinant fibrillin-1 Arg-Gly-Asp (RGD)-containing fragments PF9 and PF14. Aortic microfibrils and PF14, not PF9, substantially and dose dependently increased HUVEC cytoplasmic and nuclear calcium levels measured using the fluorescent dye Fluo-3. This effect of PF14 was confirmed in bovine aortic endothelial cells. PF14 action in HUVECs was mediated by αvβ3 and α5β1 integrins, phospholipase-C, inosital 1,4,5-trisphosphate, and mobilization of intracellular calcium stores, whereas membrane calcium channels were not or only slightly implicated, as shown in patch-clamp experiments. Finally, PF14 enhanced endothelial cell proliferation and migration. Hence, fibrillin-1 sequences may physiologically activate endothelial cells. Genetic fibrillin-1 deficiency could alter normal endothelial signaling and, since endothelium dysfunction is an important contributor to Marfan syndrome, participate in the arterial anomalies associated with this developmental disease.

Domaines

Imagerie
Fichier non déposé

Dates et versions

hal-00523374 , version 1 (05-10-2010)

Identifiants

Citer

Boubacar Mariko, Zeinab Ghandour, Stephanie Raveaud, Mickael Quentin, Yves Usson, et al.. Microfibrils and fibrillin-1 induce integrin-mediated signaling, proliferation and migration in human endothelial cells.. American Journal of Physiology - Cell Physiology, 2010, 299 (5), pp.C977-87. ⟨10.1152/ajpcell.00377.2009⟩. ⟨hal-00523374⟩
1130 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More