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DG Ryan, L Taliana, SK Masur, RM Lavker; S100A4 is Upregulated in Activated Keratocytes of the Regenerating Cornea . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2933.
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Purpose: S100A4 (mts1, p9Ka) is a member of the S100 family of calcium binding proteins. Members of the S100 subfamily have been implicated in a variety of cellular events, including growth, cell-cell communication, motility, and signal transduction. It has been suggested that S100A4 protein modulates cell motility by interacting with components of the cytoskeleton. In the present study, we investigated the distribution patterns of S100A4 in normal and regenerating corneas. Methods: A rabbit cDNA library was prepared from cultured corneal fibroblasts. The most highly abundant message was identified as S100A4. Expression of S100A4 in the cornea was determined using Northern blotting, in situ hybridization, and immunohistochemistry. Distribution patterns of S100A4 in primary corneal fibroblast cultures treated with either FGF or TGFß were analyzed by immunofluorescence. Results: S100A4 mRNA was not detected in keratocytes or epithelial cells of normal rabbit corneas. Likewise, S100A4 antigen was not present in normal mouse corneas. However, following removal of the corneal epithelium, S100A4 expression was readily detected in the stromal fibroblasts of regenerating corneas. In cultured rabbit corneal fibroblasts treated with FGF, S100A4 protein was restricted to the cytoplasm. In contrast, in cultures treated with TGFß, which induces a myofibroblast phenotype, ≷90% of the cells showed a nuclear localization of S100A4. Conclusion: Our findings suggest that S100A4 expression is upregulated in fibroblasts and myofibroblasts, the activated corneal stromal keratocytes. Its expression and subcellular distributions suggest that S100A4 may be involved in the interconversion between keratocytes, fibroblasts, and myofibroblasts during wound healing.
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