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APKC?-dependent Repression of Yap is Necessary for Functional Restoration of Irradiated Salivary Glands with IGF-1.


ABSTRACT: Xerostomia and salivary hypofunction often result as a consequence of radiation therapy for head and neck cancers, which are diagnosed in roughly 60,000 individuals every year in the U.S. Due to the lack of effective treatments for radiation-induced salivary hypofunction, stem cell-based therapies have been suggested to regenerate the irradiated salivary glands. Pharmacologically, restoration of salivary gland function has been accomplished in mice by administering IGF-1 shortly after radiation treatment, but it is not known if salivary stem and progenitor cells play a role. We show that radiation inactivates aPKC? and promotes nuclear redistribution of Yap in a population of label-retaining cells in the acinar compartment of the parotid gland (PG)- which comprises a heterogeneous pool of salivary progenitors. Administration of IGF-1 post-radiation maintains activation of aPKC? and partially rescues Yap's cellular localization in label retaining cells, while restoring salivary function. Finally, IGF-1 fails to restore saliva production in mice lacking aPKC?, demonstrating the importance of the kinase as a potential therapeutic target.

SUBMITTER: Chibly AM 

PROVIDER: S-EPMC5910385 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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aPKCζ-dependent Repression of Yap is Necessary for Functional Restoration of Irradiated Salivary Glands with IGF-1.

Chibly Alejandro M AM   Wong Wen Yu WY   Pier Maricela M   Cheng Hongqiang H   Mu Yongxin Y   Chen Ju J   Ghosh Sourav S   Limesand Kirsten H KH  

Scientific reports 20180420 1


Xerostomia and salivary hypofunction often result as a consequence of radiation therapy for head and neck cancers, which are diagnosed in roughly 60,000 individuals every year in the U.S. Due to the lack of effective treatments for radiation-induced salivary hypofunction, stem cell-based therapies have been suggested to regenerate the irradiated salivary glands. Pharmacologically, restoration of salivary gland function has been accomplished in mice by administering IGF-1 shortly after radiation  ...[more]

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