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

作者：Chibly Alejandro M; Wong Wen Yu; Pier Maricela; Cheng Hongqiang; Mu Yongxin; Chen Ju; Ghosh Sourav; Limesand Kirsten H^*

来源：Scientific Reports, 2018, 8(1): 6347.

DOI：10.1038/s41598-018-24678-4

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

• 出版日期2018-4-20