Dose-dependent response of FGF-2 for lymphangiogenesis

Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11658-63. doi: 10.1073/pnas.0404272101. Epub 2004 Aug 2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Cell Movement / drug effects
  • Cornea / blood supply
  • Cornea / physiology
  • Corneal Neovascularization
  • Dose-Response Relationship, Drug
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Fibroblast Growth Factor 2 / pharmacology*
  • Lymphangiogenesis / drug effects*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Neovascularization, Physiologic / drug effects
  • Vascular Endothelial Growth Factor C / pharmacology
  • Vascular Endothelial Growth Factor D / pharmacology

Substances

  • Vascular Endothelial Growth Factor C
  • Vascular Endothelial Growth Factor D
  • Fibroblast Growth Factor 2