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T. Onguchi, J.-H. Chang, D. T. Azar; Synergistic Effect of MT1-MMP on bFGF-Induced Corneal Angiogenesis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1493. doi: https://doi.org/.
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To evaluate the pro-angiogenic role of stromal fibroblast-derived MT1-MMP on bFGF-induced corneal angiogenesis.
We generated anti-MT1-MMP antibodies (anti-hinge:H14 and anti-cytoplasmic:C14). The expression of MT1-MMP in keratocytes and immortalized corneal fibroblast cell lines was confirmed immunohistochemically. The effect of MT1-MMP on the bFGF derived corneal vascularization was assessed by corneal micropocket assay combined with naked DNA delivery in vivo. Western blotting was used to compare signal transduction (p38, JNK, and ERK) in wild type vs MT1-MMP knock-out corneal fibroblast following bFGF stimulation.
The up-regulation of MT1-MMP after bFGF stimulation was detected in the corneal keratocyte/fibroblast using (H14 and C14 antibodies). We also confirmed the efficacy of naked plasmid DNA of MT1-MMP: The vascularized area after low dose of bFGF pellet insertion in mouse cornea was (n=6, P<0.05) significantly increased when the corneas was treated by MT1-MMP DNA transfection. The activation of p38 after bFGF stimulation on the MT1-MMP knock-out cell line was (n=3, P<0.05) significantly suppressed compared to wild type cell line.
The synergistic effect of MT1-MMP on bFGF stimulated corneal neovascularization is mediated, in part, by activation of p38 signal transduction pathway.
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