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Sci Rep. 2018 Apr 20;8(1):6347. doi: 10.1038/s41598-018-24678-4.

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

Author information

1
The University of Arizona, Cancer Biology Graduate Program, Tucson, AZ, 85721, USA.
2
The University of Arizona, Department of Nutritional Sciences, Tucson, AZ, 85721, USA.
3
University of California San Diego, School of Medicine, San Diego, CA, 92093, USA.
4
Yale University, Department of Neurology, New Haven, CT, 06511, USA.
5
The University of Arizona, Cancer Biology Graduate Program, Tucson, AZ, 85721, USA. limesank@u.arizona.edu.
6
The University of Arizona, Department of Nutritional Sciences, Tucson, AZ, 85721, USA. limesank@u.arizona.edu.

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 aPKCζ 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 aPKCζ 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 aPKCζ, demonstrating the importance of the kinase as a potential therapeutic target.

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