Effect of LYVE-1 on FGF2-induced lymphangiogenesis in vivo

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: 480 cornea: basic science • 543 growth factors/growth factor receptors