Complex changes in the apoptotic and cell differentiation programs during initiation of the hair follicle response to chemotherapy
Chemotherapy has severe side-effects for normal rapidly proliferating organs, such as hair follicle, 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 vi...
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2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227948/ |
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pubmed-42279482015-06-01 Complex changes in the apoptotic and cell differentiation programs during initiation of the hair follicle response to chemotherapy Sharova, Tatyana Y. Poterlowicz, Krzysztof Botchkareva, Natalia V. Kondratiev, Nikita A. Aziz, Ahmar Spiegel, Jeffrey H. Botchkarev, Vladimir A. Sharov, Andrey A. Article Chemotherapy has severe side-effects for normal rapidly proliferating organs, such as hair follicle, 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 and global microarray analysis was performed 3 hours after treatment. Microarray data revealed changes in expression of 504 genes in doxorubicin-treated hair follicles versus the controls. Among these genes, upregulations of several tumor necrosis factor family of apoptotic receptors (FAS, TRAIL receptors 1/2), as well as of a large number of the keratin-associated protein genes were seen after doxorubicin treatment. Hair follicle apoptosis induced by doxorubicin was significantly inhibited by either TRAIL neutralizing antibody or caspase 8 inhibitor, thus suggesting a novel role for TRAIL receptor signaling in mediating doxorubicin-induced hair loss. These data demonstrate that the early phase of the hair follicle response to doxorubicin includes upregulation of apoptosis-associated markers, as well as substantial re-organization of the terminal differentiation programs in hair follicle keratinocytes. These data provide an important platform for further studies towards the design of novel approaches for management of chemotherapy-induced hair loss. 2014-07-07 2014-12 /pmc/articles/PMC4227948/ /pubmed/24999588 http://dx.doi.org/10.1038/jid.2014.267 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Sharova, Tatyana Y. Poterlowicz, Krzysztof Botchkareva, Natalia V. Kondratiev, Nikita A. Aziz, Ahmar Spiegel, Jeffrey H. Botchkarev, Vladimir A. Sharov, Andrey A. |
| spellingShingle |
Sharova, Tatyana Y. Poterlowicz, Krzysztof Botchkareva, Natalia V. Kondratiev, Nikita A. Aziz, Ahmar Spiegel, Jeffrey H. Botchkarev, Vladimir A. Sharov, Andrey A. Complex changes in the apoptotic and cell differentiation programs during initiation of the hair follicle response to chemotherapy |
| author_facet |
Sharova, Tatyana Y. Poterlowicz, Krzysztof Botchkareva, Natalia V. Kondratiev, Nikita A. Aziz, Ahmar Spiegel, Jeffrey H. Botchkarev, Vladimir A. Sharov, Andrey A. |
| author_sort |
Sharova, Tatyana Y. |
| title |
Complex changes in the apoptotic and cell differentiation programs during initiation of the hair follicle response to chemotherapy |
| title_short |
Complex changes in the apoptotic and cell differentiation programs during initiation of the hair follicle response to chemotherapy |
| title_full |
Complex changes in the apoptotic and cell differentiation programs during initiation of the hair follicle response to chemotherapy |
| title_fullStr |
Complex changes in the apoptotic and cell differentiation programs during initiation of the hair follicle response to chemotherapy |
| title_full_unstemmed |
Complex changes in the apoptotic and cell differentiation programs during initiation of the hair follicle response to chemotherapy |
| title_sort |
complex changes in the apoptotic and cell differentiation programs during initiation of the hair follicle response to chemotherapy |
| description |
Chemotherapy has severe side-effects for normal rapidly proliferating organs, such as hair follicle, 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 and global microarray analysis was performed 3 hours after treatment. Microarray data revealed changes in expression of 504 genes in doxorubicin-treated hair follicles versus the controls. Among these genes, upregulations of several tumor necrosis factor family of apoptotic receptors (FAS, TRAIL receptors 1/2), as well as of a large number of the keratin-associated protein genes were seen after doxorubicin treatment. Hair follicle apoptosis induced by doxorubicin was significantly inhibited by either TRAIL neutralizing antibody or caspase 8 inhibitor, thus suggesting a novel role for TRAIL receptor signaling in mediating doxorubicin-induced hair loss. These data demonstrate that the early phase of the hair follicle response to doxorubicin includes upregulation of apoptosis-associated markers, as well as substantial re-organization of the terminal differentiation programs in hair follicle keratinocytes. These data provide an important platform for further studies towards the design of novel approaches for management of chemotherapy-induced hair loss. |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227948/ |
| _version_ |
1613155133206560768 |