Differential expression and localization of WNTs in an animal model of skin wound healing

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Abstract
Wound healing is a dynamic process, and a variety of growth factors have a significant impact on the process. Although the WNT family has a multitude of effects on the state of various physiological pathways, the expression and role of WNT in wounded tissue have remained an enigma. The aim of this study was to assess the expression and localization of WNTs in a murine model of wound healing. RNA isolated from full-thickness cutaneous wounds from day 1 to day 21 postwounding were subjected to reverse transcription-polymerase chain reaction, and expression of WNT3, 4, 5a, and 10b were observed. Immunohistochemistry localized WNT10b to regenerating epithelial cells on day 1 and 3, and WNT4 on day 3 and 5. WNT4 also reacted with fibroblast-like cells beneath the epithelium. The cytoplasmic staining of beta-catenin, a WNT signaling molecule, in the epithelial cells indicates an activation of the WNT signaling pathway. Among target genes downstream of the pathway, matrix metalloproteinases (MMPs) degrade and remodel the extracellular matrix during wound healing. Gelatin zymography showed that MMP9 was expressed from day 1 to day 5. MMP-2 was continuously expressed, but maximally up-regulated at day 5. Activation of MMP-2 coincided with expression of membrane-type 1 MMP, suggesting an involvement of WNTs in this proteolytic cascade. Therefore, WNTs may contribute to the process of wound healing in a spatiotemporal manner.