Pharmacological activation of the EDA/EDAR signaling pathway restores salivary gland function following radiation-induced damage.
Radiotherapy of head and neck cancers often results in collateral damage to adjacent salivary glands associated with clinically significant hyposalivation and xerostomia. Due to the reduced capacity of salivary glands to regenerate, hyposalivation is treated by substitution with artificial saliva, r...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4237357?pdf=render |
| _version_ | 1818849160574533632 |
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| author | Grace Hill Denis Headon Zoey I Harris Kenneth Huttner Kirsten H Limesand |
| author_facet | Grace Hill Denis Headon Zoey I Harris Kenneth Huttner Kirsten H Limesand |
| author_sort | Grace Hill |
| collection | DOAJ |
| description | Radiotherapy of head and neck cancers often results in collateral damage to adjacent salivary glands associated with clinically significant hyposalivation and xerostomia. Due to the reduced capacity of salivary glands to regenerate, hyposalivation is treated by substitution with artificial saliva, rather than through functional restoration of the glands. During embryogenesis, the ectodysplasin/ectodysplasin receptor (EDA/EDAR) signaling pathway is a critical element in the development and growth of salivary glands. We have assessed the effects of pharmacological activation of this pathway in a mouse model of radiation-induced salivary gland dysfunction. We report that post-irradiation administration of an EDAR-agonist monoclonal antibody (mAbEDAR1) normalizes function of radiation damaged adult salivary glands as determined by stimulated salivary flow rates. In addition, salivary gland structure and homeostasis is restored to pre-irradiation levels. These results suggest that transient activation of pathways involved in salivary gland development could facilitate regeneration and restoration of function following damage. |
| first_indexed | 2024-12-19T06:28:49Z |
| format | Article |
| id | doaj.art-3f43370647974be0a4a6a283aacf9f85 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T06:28:49Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3f43370647974be0a4a6a283aacf9f852022-12-21T20:32:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01911e11284010.1371/journal.pone.0112840Pharmacological activation of the EDA/EDAR signaling pathway restores salivary gland function following radiation-induced damage.Grace HillDenis HeadonZoey I HarrisKenneth HuttnerKirsten H LimesandRadiotherapy of head and neck cancers often results in collateral damage to adjacent salivary glands associated with clinically significant hyposalivation and xerostomia. Due to the reduced capacity of salivary glands to regenerate, hyposalivation is treated by substitution with artificial saliva, rather than through functional restoration of the glands. During embryogenesis, the ectodysplasin/ectodysplasin receptor (EDA/EDAR) signaling pathway is a critical element in the development and growth of salivary glands. We have assessed the effects of pharmacological activation of this pathway in a mouse model of radiation-induced salivary gland dysfunction. We report that post-irradiation administration of an EDAR-agonist monoclonal antibody (mAbEDAR1) normalizes function of radiation damaged adult salivary glands as determined by stimulated salivary flow rates. In addition, salivary gland structure and homeostasis is restored to pre-irradiation levels. These results suggest that transient activation of pathways involved in salivary gland development could facilitate regeneration and restoration of function following damage.http://europepmc.org/articles/PMC4237357?pdf=render |
| spellingShingle | Grace Hill Denis Headon Zoey I Harris Kenneth Huttner Kirsten H Limesand Pharmacological activation of the EDA/EDAR signaling pathway restores salivary gland function following radiation-induced damage. PLoS ONE |
| title | Pharmacological activation of the EDA/EDAR signaling pathway restores salivary gland function following radiation-induced damage. |
| title_full | Pharmacological activation of the EDA/EDAR signaling pathway restores salivary gland function following radiation-induced damage. |
| title_fullStr | Pharmacological activation of the EDA/EDAR signaling pathway restores salivary gland function following radiation-induced damage. |
| title_full_unstemmed | Pharmacological activation of the EDA/EDAR signaling pathway restores salivary gland function following radiation-induced damage. |
| title_short | Pharmacological activation of the EDA/EDAR signaling pathway restores salivary gland function following radiation-induced damage. |
| title_sort | pharmacological activation of the eda edar signaling pathway restores salivary gland function following radiation induced damage |
| url | http://europepmc.org/articles/PMC4237357?pdf=render |
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