Matrix metalloproteinase activity is necessary for thymosin beta 4 promotion of epithelial cell migration
✍ Scribed by Ping Qiu; Michelle Kurpakus-Wheater; Gabriel Sosne
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 408 KB
- Volume
- 212
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Abstract
Studies from our laboratory provide substantial evidence that thymosin beta 4, (Tβ~4~), 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 Tβ~4~‐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 Tβ~4~. GM6001, a broad‐spectrum inhibitor of active MMPs and selective MMP inhibitors, also suppressed Tβ~4~‐stimulated cell migration. Tβ~4~ 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 Tβ~4~ 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. © 2007 Wiley‐Liss, Inc.