Fibroblast Growth Factor-2 (FGF-2) Induces Vascular Endothelial Growth Factor (VEGF) Expression in the Endothelial Cells of Forming Capillaries: An Autocrine Mechanism Contributing to Angiogenesis
Autor: | Anna Gualandris, Richard L. Shapiro, Graziano Seghezzi, Giuseppe Pintucci, Daniel B. Rifkin, Aubrey C. Galloway, Edith S. Robbins, Paolo Mignatti, Sundeep Patel, Christine J. Ren |
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Jazyk: | angličtina |
Rok vydání: | 1998 |
Předmět: |
Vascular Endothelial Growth Factor A
Endothelium Angiogenesis Neovascularization Physiologic Endothelial Growth Factors Biology Fibroblast growth factor Neovascularization chemistry.chemical_compound Mice Paracrine Communication medicine Animals Humans Autocrine signalling Cells Cultured Lymphokines Vascular Endothelial Growth Factors Cell Biology Articles 3T3 Cells Recombinant Proteins Cell biology Capillaries Vascular endothelial growth factor Endothelial stem cell Vascular endothelial growth factor A Autocrine Communication medicine.anatomical_structure chemistry Cattle Fibroblast Growth Factor 2 Endothelium Vascular medicine.symptom Cell Division |
Zdroj: | The Journal of Cell Biology |
ISSN: | 1540-8140 0021-9525 |
Popis: | FGF-2 and VEGF are potent angiogenesis inducers in vivo and in vitro. Here we show that FGF-2 induces VEGF expression in vascular endothelial cells through autocrine and paracrine mechanisms. Addition of recombinant FGF-2 to cultured endothelial cells or upregulation of endogenous FGF-2 results in increased VEGF expression. Neutralizing monoclonal antibody to VEGF inhibits FGF-2–induced endothelial cell proliferation. Endogenous 18-kD FGF-2 production upregulates VEGF expression through extracellular interaction with cell membrane receptors; high-Mr FGF-2 (22–24-kD) acts via intracellular mechanism(s). During angiogenesis induced by FGF-2 in the mouse cornea, the endothelial cells of forming capillaries express VEGF mRNA and protein. Systemic administration of neutralizing VEGF antibody dramatically reduces FGF-2-induced angiogenesis. Because occasional fibroblasts or other cell types present in the corneal stroma show no significant expression of VEGF mRNA, these findings demonstrate that endothelial cell-derived VEGF is an important autocrine mediator of FGF-2-induced angiogenesis. Thus, angiogenesis in vivo can be modulated by a novel mechanism that involves the autocrine action of vascular endothelial cell-derived FGF-2 and VEGF. |
Databáze: | OpenAIRE |
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