HGF receptor up-regulation contributes to the angiogenic phenotype of human endothelial cells and promotes angiogenesis in vitro.

Institut des Vaisseaux et du Sang, Centre de Recherche de l'Association Claude Bernard, Paris, France.
Blood (Impact Factor: 9.78). 07/2003; 101(12):4816-22. DOI: 10.1182/blood-2002-06-1731
Source: PubMed

ABSTRACT Hepatocyte growth factor (HGF) is a mesenchyme-derived pleiotropic growth factor and a powerful stimulator of angiogenesis, which acts on cells by binding to the c-met receptor. The exact role of the endogenous HGF/c-met system in one or more steps of the angiogenic process is not completely understood. To contribute to this question we used immunocytochemical analysis, Western blotting, and reverse transcription-polymerase chain reaction to study the expression of c-met in endothelial cells cultured in different growth conditions. We found that c-met is not colocalized with vascular endothelial (VE)-cadherin in cell-cell junctions. c-met and VE-cadherin were shown to be inversely regulated by cell density, at both the protein and the mRNA levels. We established that c-met is up-regulated during the in vitro recapitulation of several steps of angiogenesis. The c-met expression was increased shortly after switching to angiogenic growth conditions and remained high during the very first steps of angiogenesis, including cell migration, and cell proliferation. The endothelial cells in which the expression of c-met was up-regulated were more responsive to HGF and exhibited a higher rate of morphogenesis. Moreover, the antibody directed against the extracellular domain of the c-met inhibited angiogenesis in vitro. Our results suggest that c-met is a marker of angiogenic phenotype for endothelial cells and represents an attractive target for the development of new antiangiogenic therapies.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The survival of tissue-engineered mucosa (TEM) after implantation is mostly dependent on the presence of blood vessels for continuous oxygen supply. Therefore the stimulation of vascularization of TEM is essential to improve survival in vivo. Hyperbaric oxygen treatment (HBO), used to improve wound healing, stimulates the secretion of angiogenic factors. In this study we evaluated the effect of daily HBO treatments on TEM for 1, 3 or 5 consecutive days. Overall histology with hematoxylin-eosin staining showed no apparent changes after 1 treatment. After 3 and 5 HBO treatments, the basal layer became irregular and pyknotic cells were observed. Measurements of the viable epithelium showed significant thinning after 1 and 5 treatments, however proliferation was not affected. The angiogenic factors keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), basic fibroblast growth factor (FGFbasic), and placental growth factor (PlGF) were significantly increased after 1 HBO treatment, whereas after 3 treatments a significant decrease of FGFbasic and PlGF was seen. After 5 treatments KGF, PlGF and vascular endothelial growth factor (VEGF) were significantly increased. One HBO treatment of TEM enhances the secretion of important angiogenic factors, hereby potentially improving the survival rate after in vivo implantation.
    Tissue Engineering Part A 12/2013; · 4.64 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Heparan sulfate (HS), a long linear polysaccharide of alternating disaccharide residues, interacts with a wide variety of proteins, including many angiogenic factors. The involvement of HS in signaling of pro-angiogenic factors (e.g. vascular endothelial growth factor and fibroblast growth factor 2), as well as interaction with anti-angiogenic factors (e.g. endostatin), warrants its role as an important modifier of (tumor) angiogenesis. This review summarizes our current understanding of the role of HS in angiogenic growth factor signaling, and discusses therapeutic strategies to target HS and modulate angiogenesis.
    Angiogenesis 10/2013; · 4.41 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Stem cell therapy has shown promise in treating a variety of pathologies including skin wounds, but practical applications remain elusive. Here we demonstrate that endogenous stem cell mobilization produced by AMD3100 and low-dose Tacrolimus is able to reduce by 25% the time of complete healing of full-thickness wounds created by surgical excision. Equally important, healing was accompanied by reduced scar and regeneration of hair follicles. Searching for mechanisms, we found that AMD3100 combined with low-dose Tacrolimus mobilized increased number of lineage-negative c-Kit+, CD34+ and CD133+ stem cells. Low-dose Tacrolimus also increased the number of SDF-1 bearing macrophages in the wounds sites amplifying the "pull" of mobilized stem cells into the wound. Lineage tracing demonstrated the critical role of CD133 stem cells in enhanced capillary and hair follicle neogenesis contributing to more rapid and perfect healing. Our findings offer a significant therapeutic approach to wound healing and tissue regeneration.Journal of Investigative Dermatology accepted article preview online, 28 March 2014; doi:10.1038/jid.2014.162.
    Journal of Investigative Dermatology 03/2014; · 6.19 Impact Factor