Dose-dependent response of FGF-2 for lymphangiogenesis.
Spatio-temporal studies on the growth of capillary blood vessels and capillary lymphatic vessels in tissue remodeling have suggested that lymphangiogenesis is angiogenesis-dependent. We revisited this concept by using fibroblast growth factor 2 (FGF-2) (80 ng) to stimulate the growth of both vessel types in the mouse cornea. When we lowered the dose of FGF-2 in the cornea 6.4-fold (12.5 ng), the primary response was lymphangiogenic. Further investigation revealed that vascular endothelial growth factor-C and -D are required for this apparent lymphangiogenic property of FGF-2, and when the small amount of accompanying angiogenesis was completely suppressed, lymphangiogenesis remained unaffected. Our findings demonstrate that there is a dose-dependent response of FGF-2 for lymphangiogenesis, and lymphangiogenesis can occur in the absence of a preexisting or developing vascular bed, i.e., in the absence of angiogenesis, in the mouse cornea.
Chang
Lynn K
LK
Vascular Biology Program, Department of Surgery, Children's Hospital Boston, Boston, MA 02115, USA.
Garcia-Cardeña
Guillermo
G
Farnebo
Filip
F
Fannon
Michael
M
Chen
Emy J
EJ
Butterfield
Catherine
C
Moses
Marsha A
MA
Mulligan
Richard C
RC
Folkman
Judah
J
Kaipainen
Arja
A
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003315:Cornea / Q000098:blood supply / Q000502:physiology; D016510:Corneal Neovascularization; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D042583:Lymphangiogenesis / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018919:Neovascularization, Physiologic / Q000187:drug effects; D042582:Vascular Endothelial Growth Factor C / Q000494:pharmacology; D042643:Vascular Endothelial Growth Factor D / Q000494:pharmacology
D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D016222:Fibroblast Growth Factor 2