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Identification of novel AP-1 target genes in fibroblasts regulated during cutaneous wound healing

Oncogene volume 23, pages 7005–7017 (2004)Cite this article

Abstract

Mesenchymal–epithelial interactions are increasingly considered to be of vital importance for epithelial homeostasis and regeneration. In skin, the transcription factor AP-1 was shown to be critically involved in the communication between keratinocytes and dermal fibroblasts. After skin injury, the release of IL-1 from keratinocytes induces the activity of the AP-1 subunits c-Jun and JunB in fibroblasts leading to a global change in gene expression. To identify AP-1 target genes in fibroblasts, which are involved in the process of cutaneous repair, we performed gene expression profiling of wild-type, c-jun- and junB-deficient fibroblasts in response to IL-1, mimicking the initial phase of wound healing. Using a 15K cDNA collection, over 1000 genes were found to be Jun-dependent and additional 300 clones showed IL-1 responsiveness. Combinatorial evaluation allowed for the dissection of the specific contribution of either AP-1 subunit to gene regulation. Besides previously identified genes that are involved in cutaneous repair, we have identified novel genes regulated during wound healing in vivo and showed their expression by fibroblasts on wound sections. The identification of novel Jun target genes should provide a basis for understanding the molecular mechanisms underlying mesenchymal–epithelial interactions and the critical contribution of AP-1 to tissue homeostasis and repair.

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Acknowledgements

We thank Dr Jochen Hess for careful proofreading of the manuscript. This work was supported by the Deutsche Forschungsgemeinschaft (An 182/8-2) and by the Research Training Network (RTN) Program of the European Community.

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Authors and Affiliations

  1. Division of Signal Transduction and Growth Control, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, Heidelberg, D-69120, Germany

    Lore Florin, Bernd Thilo Dittrich, Sabine Gack, Marina Schorpp-Kistner, Axel Szabowski & Peter Angel

  2. Division of Molecular Genetics, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, Heidelberg, D-69120, Germany

    Lars Hummerich, Felix Kokocinski, Gunnar Wrobel, Meinhard Hahn & Peter Lichter

  3. Institute of Cell Biology, ETH Zuerich, Hoenggerberg, Zuerich, CH-8093, Switzerland

    Sabine Werner

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  1. Lore Florin
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Correspondence to Peter Angel.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc).

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Florin, L., Hummerich, L., Dittrich, B. et al. Identification of novel AP-1 target genes in fibroblasts regulated during cutaneous wound healing. Oncogene 23, 7005–7017 (2004). https://doi.org/10.1038/sj.onc.1207938

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