Fas signaling is involved in the control of hair follicle response to chemotherapy
Fas signaling is involved in the control of hair follicle response to chemotherapy
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DOI：
10.1158/0008-5472.can-04-1367
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发表时间：
2004-09-01
期刊：
影响因子：
11.2
通讯作者：
Botchkarev, VA
中科院分区：
文献类型：
--
作者：
Sharov, AA;Siebenhaar, F;Botchkarev, VA
化疗药物诱导毛囊（HF）中的p53依赖性细胞凋亡，导致脱发，这是癌症治疗的常见副作用。在这里，我们表明，Fas作为p53的目标发挥重要作用的HF响应环磷酰胺。具体来说，我们证明，Fas上调后，在HF角质形成细胞环磷酰胺治疗，Fas配体中和抗体部分抑制HF反应，环磷酰胺在野生型小鼠，Fas基因敲除小鼠表现出显着的延迟环磷酰胺诱导的HIT退化与减少Fas相关的死亡结构域和caspase-8的表达。这些数据提出了一种可能性，探讨阻断Fas信号作为一个复杂的局部治疗的一部分，抑制角质形成细胞凋亡和化疗引起的脱发。
Chemotherapeutic agents induce p53-dependent apoptosis in the hair follicle (HF) resulting in hair loss, a common side effect of cancer therapy. Here, we show that Fas as a p53 target plays important role in the HF response to cyclophosphamide. Specifically, we demonstrate that Fas is up-regulated in HF keratinocytes after cyclophosphamide treatment, Fas ligand-neutralizing antibody partially inhibits HF response to cyclophosphamide in wild-type mice, and Fas knockout mice show significant retardation of cyclophosphamide-induced HIT involution associated with reduced Fas-associated death domain and caspase-8 expression. These data raise a possibility to explore blockade of Fas signaling as a part of complex local therapy for inhibiting keratinocyte apoptosis and hair loss induced by chemotherapy.