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    Complex Changes in the Apoptotic and Cell Differentiation Programs during Initiation of the Hair Follicle Response to Chemotherapy

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    Publication date
    2014
    Author
    Sharova, T.Y.
    Poterlowicz, Krzysztof
    Botchkareva, Natalia V.
    Kondratiev, N.A.
    Aziz, A.
    Spiegel, J.H.
    Botchkarev, Vladimir A.
    Sharov, A.A.
    Keyword
    Chemotherapy
    ; Hair follicles
    ; Apoptosis
    ; Doxorubicin
    Peer-Reviewed
    Yes
    
    Metadata
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    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 apoptosisinducing 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.
    URI
    http://hdl.handle.net/10454/6726
    Version
    No full-text in the repository
    Citation
    Sharova TY, Poterlowicz K, Botchkareva NV et al (2014) Complex Changes in the Apoptotic and Cell Differentiation Programs during Initiation of the Hair Follicle Response to Chemotherapy. Journal of Investigative Dermatology. 134(12): 2873-2882.
    Link to publisher’s version
    http://dx.doi.org/10.1038/jid.2014.267
    Type
    Article
    Collections
    Life Sciences Publications

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