Fas signaling is involved in the control of hair follicle response to chemotherapy.
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 HF 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.
Sharov
Andrei A
AA
Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Siebenhaar
Frank
F
Sharova
Tatyana Y
TY
Botchkareva
Natalia V
NV
Gilchrest
Barbara A
BA
Botchkarev
Vladimir A
VA
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002352:Carrier Proteins / Q000096:biosynthesis; D053181:Caspase 8; D020169:Caspases / Q000096:biosynthesis; D003520:Cyclophosphamide / Q000494:pharmacology*; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D005260:Female; D018859:Hair Follicle / Q000187:drug effects* / Q000502:physiology*; D020287:In Situ Nick-End Labeling; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction; D019014:fas Receptor / Q000378:metabolism / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; D018906:Antineoplastic Agents, Alkylating; D002352:Carrier Proteins; C505534:Fadd protein, mouse; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor; D003520:Cyclophosphamide; C505526:Casp8 protein, mouse; D053181:Caspase 8; D020169:Caspases