Retroductal Delivery of Epidermal Growth Factor Protects Salivary Progenitors after Irradiation

J. M. Cho, Y. J. Yoon, S. Lee, D. Kim, D. Choi, J. Kim, J. Y. Lim

Research output: Contribution to journalArticlepeer-review

Abstract

Salivary gland hypofunction after irradiation is associated with a deficit of epithelial stem/progenitors in salivary glands. Although epidermal growth factor (EGF) is known to stimulate the proliferation of epithelial cells, the therapeutic effect of EGF on salivary epithelial stem/progenitors remains undetermined. In this study, we administered EGF to submandibular glands (SMGs) via a retrograde route through the SMG excretory duct before fractionated irradiation and examined whether EGF could protect salivary epithelial progenitor cells from radiation and alleviate radiation-induced salivary hypofunction. EGF-treated mice exhibited greater body and gland weights at 12 wk after irradiation than untreated mice. The retroductal delivery of EGF improved salivary secretory function and increased salivary amylase activity in a dose-dependent manner. Histological examinations highlighted the amelioration of the loss of keratine-14+ (KRT14+) basal ductal and/or MIST1+ acinar cells, as well as induction of fibrosis, following irradiation in EGF-treated mice. An additional in vitro experiment using a salivary gland organoid irradiation model indicated that the radioprotective effects of EGF promoted the growth and inhibited the apoptotic cell death of salivary epithelial cells. Our results suggest that retroductal delivery of EGF may be a promising therapeutic option for preventing radiation-induced salivary gland hypofunction.

Original languageEnglish
Pages (from-to)883-890
Number of pages8
JournalJournal of Dental Research
Volume100
Issue number8
DOIs
Publication statusPublished - 2021 Jul

Bibliographical note

Funding Information:
We are grateful to the Yonsei-Carl Zeiss Advanced Imaging Center and Yonsei-Flow Cytometry Core Facility in Yonsei University College of Medicine for their technical assistance. The R-spondin 1 conditioned medium and WNT3A conditioned medium were kindly provided by Prof. Hyun Ki Kim?s laboratory (Yonsei University College of Medicine). The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning (NRF-2018R1A2 B3004269 and NRF-2020M3A9I4039045, Republic of Korea).

Funding Information:
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning (NRF-2018R1A2 B3004269 and NRF-2020M3A9I4039045, Republic of Korea).

Publisher Copyright:
© International & American Associations for Dental Research 2021.

All Science Journal Classification (ASJC) codes

  • Dentistry(all)

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