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Birgit Regenfuss, Natalia Platonova, Géraldine Miquel, Said Taouji, Eric Chevet, Andreas Bikfalvi, Claus Cursiefen; Effect of LYVE-1 on FGF2-induced lymphangiogenesis in vivo. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2100.
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Hyaluronan receptor LYVE-1 (lymphatic vessel endothelial hyaluronan receptor-1) is expressed mainly on the surface of lymphatic endothelium and is involved in binding and internalization of the extracellular matrix glycosaminoglycan hyaluronan. However it was recently shown that LYVE-1-deleted mice have no obvious structural or functional lymphatic defects and normal hyaluronan levels. As the interplay between hyaluronan receptor CD44, a close homologue of LYVE-1, and the growth-factor FGF2 is already known, a possible interaction of LYVE-1 with FGF2 and its effect on lymphatic vasculature was analyzed in this study.
The mouse corneal micropocket assay was performed with sucralfate pellets containing a combination of 80 ng recombinant human FGF2 (rhFGF2) or 200 ng rhVEGF-C respectively and 1 µg recombinant human LYVE-1. Control pellets contained 80 ng rhFGF-2 or 200 ng rhVEGF-C alone. Pellets were coated with hydron and implanted into a corneal micropocket. On postoperative day seven the mice were euthanized, the cornea with limbus was excised and the lymphangiogenic response was analyzed semiautomatically.
Treatment of corneas with pellets containing the combination of FGF2/LYVE-1 resulted in the outgrowth of lymphatic vessels with a mean neovascularization area of 0.12 ± 0.07 mm2 (n=20) whereas corneas with pellets containing FGF2 alone showed a mean neovascularization area of 0.23 ± 0.11 mm2 (n=21) (p = 0.0008). Contrary no significant difference was found between VEGF-C induced lymphangiogenesis and the combination of VEGF-C/LYVE-1 induced lymphangiogenesis in the micropocket assay.
LYVE-1 inhibited the FGF2-induced outgrowth of lymphatic vessels in a corneal micropocket assay suggesting that LYVE-1 may bind FGF2 and interact with bFGF influencing lymphangiogenesis in vivo.
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