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ephrin-b reverse signaling induces expression of wound healing associated genes in IEC-6 intestinal epithelial cells

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World Journal of Gastroenterology 2005年第29期11卷 4511-4518页

作者： Christian Hafner Stefanie Meyer Ilja Hagen bernd becker Alexander Roesch Michael Landthaler Thomas Vogt Department of Dermatology University Hospital of Regensburg Regensburg D-93042 Germany

AIM： Eph receptors and ephrin ligands play a pivotal role in development and tissue maintenance. Since previous data have indicated an involvement of ephrin-b2 in epithelial healing, we investigated the gene expression and downstream signaling pathways induced by ephrin-b mediated cell-cell signaling in intestinal epithelial cells. METHODS： Upon stimulation of ephrin-b pathways in IEC-6 cells with recombinant rat Ephb1-Fc, gene expression was analyzed by Affymetrix rat genome 230 high density arrays at different time points. Differentially expressed genes were confirmed by real-time RT-PCR. In addition, MAP kinase pathways and focal adhesion kinase （FAK） activation downstream of ephrin-b were investigated by immunoblotting and fluorescence microscopy. RESULTS： Stimulation of the ephrin-b reverse signaling pathway in IEC-6 cells induces predominant expression of genes known to be involved into wound healing/cell migration, antiapoptotic pathways, host defense and inflammation. Cox-2, c-Fos, Egr-1, Egr-2, and MCP-1 were found among the most significantly regulated genes. Furthermore, we show that the expression of repair- related genes is also accompanied by activation of the ERKI/2 MAP kinase pathway and FAK, two key regulators of epithelial restitution. CONCLUSION： Stimulation of the ephrin-b reverse signaling pathway induces a phenotype characterized by upregulation of repair-related genes, which may partially be mediated by ERK1/2 pathways.

关键词： ephrin-b IEC-6 Wound healing Gene expression c-Fos Egr-1/2 COX-2

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