Connective tissue growth factor binds vascular endothelial growth factor (VEGF) and inhibits VEGF‐induced angiogenesis

  title={Connective tissue growth factor binds vascular endothelial growth factor (VEGF) and inhibits VEGF‐induced angiogenesis},
  author={Isao Inoki and Takayuki Shiomi and Gakuji Hashimoto and Hiroyuki Enomoto and Hiroyuki Nakamura and Ken-ichi Makino and Eiji Ikeda and Shigeo Takata and Ken-ichi Kobayashi and Yasunori Okada},
  journal={The FASEB Journal},
Vascular endothelial growth factor (VEGF) is a strong angiogenic mitogen and plays important roles in angiogenesis under various pathophysiological conditions. The in vivo angiogenic activity of secreted VEGF may be regulated by extracellular inhibitors, because it is also produced in avascular tissues such as the cartilage. To seek the binding inhibitors against VEGF, we screened the chondrocyte cDNA library by a yeast two‐hybrid system by using VEGF165 as bait and identified connective tissue… 

Heparin affin regulatory peptide binds to vascular endothelial growth factor (VEGF) and inhibits VEGF-induced angiogenesis

In vivo studies showed that HARP inhibited the VEGF165-induced Matrigel™ infiltration of endothelial cells, and data demonstrate for the first time that the angiogenic factor HARP can also negatively regulates theAngiogenic activity of V EGF165.

Regulation of angiogenesis and endothelial cell function by connective tissue growth factor (CTGF) and cysteine-rich 61 (CYR61)

There is strong evidence supporting a role for CTGF and CYR61 in the regulation of endothelial cell function and angiogenesis, as well as participating in the angiogenic process during embryonic development, placentation, tumor formation, fibrosis, and wound healing.

Effect of connective tissue growth factor on hypoxia-inducible factor 1alpha degradation and tumor angiogenesis.

CTGF inhibition of metastasis involves the inhibition of VEGF-A-dependent angiogenesis, possibly by promoting HIF-1alpha protein degradation in CTGF-overexpressing cells.

VEGF-A/VEGFR2 signaling network in endothelial cells relevant to angiogenesis

This work has developed the first comprehensive map of endothelial cell-specific signaling events of VEGFA/VEGFR2 system pertaining to angiogenesis and believes that this map would serve as a novel platform for reference, integration, and representation and more significantly, the progressive analysis of dynamic features of V EGF signaling in endothelial cells including their cross-talks with other ligand-receptor systems involved inAngiogenesis.

Matrix Metalloproteinases Cleave Connective Tissue Growth Factor and Reactivate Angiogenic Activity of Vascular Endothelial Growth Factor 165*

It is demonstrated for the first time that CTGF is a substrate of MMPs and that the angiogenic activity of VEGF165 suppressed by the complex formation withCTGF is recovered through the selective degradation of CTGF by M MPs.

Fibulin-5 antagonizes vascular endothelial growth factor (VEGF) signaling and angiogenic sprouting by endothelial cells.

It is shown that TGF-beta stimulates FBLN-5 expression in endothelial cells, and that this response was inhibited by coadministration of the proangiogenic factor, VEGF, and the ability of FBLn-5 to antagonize angiogenic processes was determined to be independent of its integrin-binding RGD motif.

Connective Tissue Growth Factor Regulates Retinal Neovascularization through p53 Protein-dependent Transactivation of the Matrix Metalloproteinase (MMP)-2 Gene*

This work shows that CTGF/CCN2 was dynamically expressed in the developing murine retinal vasculature and was abnormally increased and localized within neovascular tufts in the mouse eye with oxygen-induced retinopathy, and provided the rational basis for targeting the p53 pathway to curtail the effects of CTGF or CCN2 on neovessel formation associated with ischemic retinitis.

Connective-tissue growth factor (CTGF) modulates cell signalling by BMP and TGF-β

Results show that CTGF inhibits BMP and activates TGF-β signals by direct binding in the extracellular space and can antagonize BMP4 activity by preventing its binding to BMP receptors and has the opposite effect, enhancement of receptor binding, on T GF-β1.



Vascular endothelial growth factor (VEGF) and its receptors

Recent developments that have widened considerably the understanding of the mechanisms that control V EGF production and VEGF signal transduction are focused on and recent studies that have shed light on the mechanisms by which VEGf regulates angiogenesis are reviewed.

Connective tissue growth factor induces the proliferation, migration, and tube formation of vascular endothelial cells in vitro, and angiogenesis in vivo.

Findings indicate that CTGF is a novel, potent angiogenesis factor which functions in multi-stages in this process.

VEGF121, a vascular endothelial growth factor (VEGF) isoform lacking heparin binding ability, requires cell-surface heparan sulfates for efficient binding to the VEGF receptors of human melanoma cells

Results suggest that cell-surface heparan sulfates may regulate the binding ability of the VEGF receptors of the melanoma cells and indicate that heparin is not able to fully substitute for cell surface-associated heparAn sulfates.

The vascular endothelial growth factor (VEGF) isoforms: differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF.

VEGF associated with the ECM was bioactive, because endothelial cells cultured on ECM derived from cells expressing VEGF189 or V EGF206 were markedly stimulated to proliferate and can be released into a soluble and bioactive form by heparin or plasmin.

Vascular Endothelial Growth Factor Induces Expression of Connective Tissue Growth Factor via KDR, Flt1, and Phosphatidylinositol 3-Kinase-Akt-dependent Pathways in Retinal Vascular Cells*

It is suggested that VEGF can increase CTGF gene expression in bovine retinal capillary cells via KDR or Flt receptors and the activation of PI3-kinase-Akt pathway independently of PKC or Ras-ERK pathway, possibly inducing the fibrosis observed in retinal neovascular diseases.

Paracrine expression of a native soluble vascular endothelial growth factor receptor inhibits tumor growth, metastasis, and mortality rate.

Results not only support VEGF receptors as antiangiogenic targets but also demonstrate that sflt-1 gene therapy might be a feasible approach for inhibiting tumor angiogenesis and growth.

Vascular endothelial growth factor is a secreted angiogenic mitogen.

DNA sequencing suggests the existence of several molecular species of VEGF, a heparin-binding growth factor specific for vascular endothelial cells that is able to induce angiogenesis in vivo.

Vascular endothelial growth factor (VEGF) in cartilage neovascularization and chondrocyte differentiation: auto-paracrine role during endochondral bone formation.

It is proposed that VEGF is actively responsible for hypertrophic cartilage neovascularization through a paracrine release by chondrocytes, with invading endothelial cells as a target.

Molecular and biological properties of vascular endothelial growth factor

  • N. Ferrara
  • Biology
    Journal of Molecular Medicine
  • 1999
Current evidence indicates that VEGF is essential for embryonic vasculogenesis and angiogenesis, and both therapeuticAngiogenesis using recombinant V EGF or VEGFs gene transfer and inhibition of VEGf-mediated pathological angiogenic are being pursued.