Angiogenesis stimulated by PDGF-CC, a novel member in the PDGF family, involves activation of PDGFR-alphaalpha and -alphabeta receptors.
A newly discovered PDGF isoform, PDGF-CC, is expressed in actively angiogenic tissues such as placenta, some embryonic tissues, and tumors. We test the possibility that PDGF-CC promotes angiogenesis in vivo. The core domain (mature form) of human PDGF-CC is sufficiently potent to stimulate neovascularization in the mouse cornea. The corneal angiogenic response induced by PDGF-CC is robust although the area of neovascularization is smaller than those of FGF-2- and VEGF-stimulated angiogenesis. Similarly, PDGF-BB and PDGF-AB induce angiogenic responses virtually indistinguishable from PDGF-CC-stimulated vessels. In contrast, PDGF-AA displays only a weak angiogenic response in the mouse cornea. Although there was no significant difference in incorporation of mural cells to the newly formed blood vessels induced by PDGF-BB and -CC, the percentage of mural cell positive vessels induced by PDGF-AA was greater than those induced by FGF-2, PDGF-BB, and PDGF-CC. In the developing chick embryo, PDGF-CC induced branch sprouts from established blood vessels. In PDGF receptor-transfected endothelial cells, PDGF-CC activated the PDGF receptor alpha subunit (PDGFR-alpha). PDGF-CC, but not PDGF-AA, was able to activate PDGFR-beta receptor in endothelial cells that coexpress both alpha and beta forms of receptors. Thus, the PDGF-CC-mediated angiogenic response is most likely transduced by PDGF-alphaalpha and -alphabeta receptors. These data demonstrate that the PDGF family is a complex and important group of proangiogenic factors.
Cao
Renhai
R
Microbiology and Tumor Biology Center, Karolinska Institute, S-171 77 Stockholm, Sweden.
Bråkenhielm
Ebba
E
Li
Xuri
X
Pietras
Kristian
K
Widenfalk
Johan
J
Ostman
Arne
A
Eriksson
Ulf
U
Cao
Yuhai
Y
D000482:Allantois / Q000098:blood supply / Q000187:drug effects; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply / Q000187:drug effects; D003315:Cornea / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008222:Lymphokines / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D010982:Platelet-Derived Growth Factor; D020033:Protein Isoforms; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C411423:platelet-derived growth factor C; D014443:Tyrosine; D020796:Receptor, Platelet-Derived Growth Factor alpha