title: Complex changes in the apoptotic and cell differentiation programs during initiation of the hair follicle response to chemotherapy.
abstract: Chemotherapy has severe side effects in normal rapidly proliferating organs, such as hair follicles, and causes massive apoptosis in hair matrix keratinocytes followed by hair loss. To define the molecular signature of hair follicle response to chemotherapy, human scalp hair follicles cultured ex vivo were treated with doxorubicin (DXR), and global microarray analysis was performed 3 hours after treatment. Microarray data revealed changes in expression of 504 genes in DXR-treated hair follicles versus controls. Among these genes, upregulations of several tumor necrosis factor family of apoptotic receptors (FAS, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) receptors 1/2), as well as of a large number of keratin-associated protein genes, were seen after DXR treatment. Hair follicle apoptosis induced by DXR was significantly inhibited by either TRAIL-neutralizing antibody or caspase-8 inhibitor, thus suggesting a previously unreported role for TRAIL receptor signaling in mediating DXR-induced hair loss. These data demonstrate that the early phase of the hair follicle response to DXR includes upregulation of apoptosis-associated markers, as well as substantial reorganization of the terminal differentiation programs in hair follicle keratinocytes. These data provide an important platform for further studies toward the design of effective approaches for the management of chemotherapy-induced hair loss.
authors.affiliation: Departments of Dermatology, Boston University School of Medicine, Boston, Massachusetts, USA; Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Tatyana Y
authors.initials: TY
authors.lastname: Sharova
authors.affiliation: Centre for Skin Sciences, School of Life Sciences, University of Bradford, Bradford, UK.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Poterlowicz
authors.affiliation: Centre for Skin Sciences, School of Life Sciences, University of Bradford, Bradford, UK.
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Botchkareva
authors.affiliation: Departments of Dermatology, Boston University School of Medicine, Boston, Massachusetts, USA; Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Nikita A
authors.initials: NA
authors.lastname: Kondratiev
authors.affiliation: Departments of Dermatology, Boston University School of Medicine, Boston, Massachusetts, USA; Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Ahmar
authors.initials: A
authors.lastname: Aziz
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Spiegel
authors.affiliation: Departments of Dermatology, Boston University School of Medicine, Boston, Massachusetts, USA; Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts, USA; Centre for Skin Sciences, School of Life Sciences, University of Bradford, Bradford, UK. Electronic address: v.a.botchkarev@bradford.ac.uk.
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Botchkarev
authors.affiliation: Departments of Dermatology, Boston University School of Medicine, Boston, Massachusetts, USA; Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts, USA. Electronic address: drsharov@bu.edu.
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Sharov
mesh_terms: D000505:Alopecia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8 / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects; D004317:Doxorubicin / Q000009:adverse effects / Q000494:pharmacology*; D018859:Hair Follicle / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019014:fas Receptor / Q000187:drug effects / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D019014:fas Receptor; D004317:Doxorubicin; D053181:Caspase 8