No / 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.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/6726 |
| Date | 07 August 2014 |
| Creators | Sharova, T.Y., Poterlowicz, Krzysztof, Botchkareva, Natalia V., Kondratiev, N.A., Aziz, A., Spiegel, J.H., Botchkarev, Vladimir A., Sharov, A.A. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, No full-text in the repository |
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