Letter abstract
Nature Cell Biology
Published online: 20 July 2008 | doi:10.1038/ncb1761
Epidermal JunB represses G-CSF transcription and affects haematopoiesis and bone formation
Arabella Meixner1,3,7, Rainer Zenz1,4,7, Helia B Schonthaler1,6, Lukas Kenner1,4,5, Harald Scheuch1, Josef M. Penninger2 & Erwin F. Wagner1,6
Mice that lack JunB in epidermal cells are born with normal skin; however, keratinocytes hyperproliferate in vitro and on TPA treatment in vivo. Loss of JunB expression in the epidermis of adult mice affects the skin, the proliferation of haematopoietic cells and bone formation. G-CSF is a direct transcriptional target of JunB and mutant epidermis releases large amounts of G-CSF that reach high systemic levels and cause skin ulcerations, myeloproliferative disease and low bone mass. The absence of G-CSF significantly improves hyperkeratosis and prevents the development of myeloproliferative disease, but does not affect bone loss. This study describes a mechanism by which the absence of JunB in epithelial cells causes multi-organ disease, suggesting that the epidermis can act as an endocrine-like organ.
- Research Institute of Molecular Pathology (IMP), Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
- Institute of Molecular Biotechnology (IMBA), Dr. Bohr-Gasse 3, A-1030 Vienna, Austria.
- Current addresses: Institute of Molecular Biotechnology (IMBA), Dr. Bohr-Gasse 3, A-1030 Vienna, Austria;
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Ludwig Boltzmann Institute for Cancer Research (LBI-CR), Währingerstra
e 13a, A-1090 Vienna, Austria; - Institute of Clinical Pathology, Medical University of Vienna, Währingergürtel 18-20, A-1090 Vienna, Austria.
- Cancer Cell Biology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Melchor Fernández Almagro, 3, E-28029 Madrid, Spain.
- These authors contributed equally to this work.
Correspondence to: Erwin F. Wagner1,6 e-mail: ewagner@cnio.es