Matrix metalloproteinase activity is necessary for thymosin beta 4 promotion of epithelial cell migration

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Abstract
Studies from our laboratory provide substantial evidence that thymosin beta 4, (Tβ4), an actin-sequestering protein, promotes corneal wound healing through its ability to stimulate epithelial cell migration. Matrix metalloproteinases (MMPs), which are expressed in a wide variety of tissues including the cornea, also play a key role in epithelial cell migration and wound healing. In this study we investigated the role of MMPs in Tβ4-stimulated corneal epithelial cell migration. In Boyden chamber assays, XG076, an inhibitor of the conversion of pro- to active MMPs, had no effect on epithelial cell migration stimulated by exogenous activated MMP-1. However, in in vitro migration assays where the activation of pro-MMPs was blocked, XG076 significantly inhibited cell migration and wound healing in the presence or absence of Tβ4. GM6001, a broad-spectrum inhibitor of active MMPs and selective MMP inhibitors, also suppressed Tβ4-stimulated cell migration. Tβ4 upregulated MMP-1 gene and protein expression in primary human corneal epithelial cells and in transformed human corneal epithelial cells following scrape wounding. From these results we conclude that MMP catalytic activity is necessary for Tβ4 promotion of epithelial cell migration. These novel findings are the first to demonstrate a functional link between the two. J. Cell. Physiol. 212: 165–173, 2007.

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