Digital gene expression profiling of mouse skin gene expression after cyclophosphamide (CYP) treatment
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ABSTRACT: Chemotherapy often causes adverse effects including hair loss, however, the molecular basis remains unclear. A common assumption is that by targeting actively dividing cancer cells, chemo-drugs would inevitably damage normal proliferating cells as a “side effect”. Using both mouse hair and avian feather as models, here we show that down-regulation of sonic hedgehog (Shh) signaling is a critical event mediating chemo-drug induced tissue damage. Reduced expression of Shh is also apparent in human patients who experience hair loss after receiving chemotherapy, and in animal models treated with several frontline chemo-drugs. Supplementation of Shh protein or steroid hormones that activate Shh signaling prevented hair loss, but interestingly, not the damage to the pigment system. Together, our results have elucidated a molecular mechanism underlying chemotherapy-induced tissue damage, and suggested novel concepts and methodologies for future clinical interventions and drug development.
ORGANISM(S): Mus musculus
PROVIDER: GSE41287 | GEO | 2017/01/01
SECONDARY ACCESSION(S): PRJNA176731
REPOSITORIES: GEO
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