C-KIT, by interacting with the membrane-bound ligand, recruits endothelial progenitor cells to inflamed endothelium.
We investigated the role of c-Kit and the membrane-bound ligand (mbKitL) in endothelial progenitor cell (EPC) recruitment by microvascular endothelial cells (ECs). We demonstrated that inflammatory activation induced the expression of the mbKitL on ECs both in vitro and in vivo, and that recruitment of EPCs depended on c-Kit/mbKitL interaction. Depletion of endogenous c-Kit or inhibition of c-Kit enzymatic activity by imatinib mesylate prevented adhesion of EPCs to activated ECs both in vitro and in vivo, indicating that a functional c-Kit on EPCs is essential. We also demonstrate that Akt was the downstream molecule regulating cell adhesion. A potential role of the c-Kit/mbKitL interaction in pathological settings is sustained by the expression of the mbKitL on ECs lining intraplaque neovessels. Thus, our results provide new insights into the mechanisms underlying EPC recruitment and the bases for novel strategies to hinder pathological angiogenesis.
Dentelli
Patrizia
P
Department of Internal Medicine, University of Turin, Italy.
Rosso
Arturo
A
Balsamo
Antonina
A
Colmenares Benedetto
Sofia
S
Zeoli
Annarita
A
Pegoraro
Marco
M
Camussi
Giovanni
G
Pegoraro
Luigi
L
Brizzi
Maria Felice
MF
D000818:Animals; D002448:Cell Adhesion; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009389:Neovascularization, Pathologic / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000502:physiology; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism* / Q000502:physiology*; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*
D008565:Membrane Proteins; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit; D051058:Oncogene Protein v-akt