Epidermal JunB represses G-CSF transcription and affects haematopoiesis and bone formation.
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.
Meixner
Arabella
A
Research Institute of Molecular Pathology (IMP), Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
Zenz
Rainer
R
Schonthaler
Helia B
HB
Kenner
Lukas
L
Scheuch
Harald
H
Penninger
Josef M
JM
Wagner
Erwin F
EF
D000818:Animals; D004817:Epidermis; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics*; D006410:Hematopoiesis; D051379:Mice; D008817:Mice, Mutant Strains; D010012:Osteogenesis; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D012097:Repressor Proteins; D014158:Transcription, Genetic
D016755:Proto-Oncogene Proteins c-jun; D012097:Repressor Proteins; D016179:Granulocyte Colony-Stimulating Factor