Management of salivary gland hypofunction caused by irradiation (IR) therapy for head and neck cancer remains lack of effective treatments. Salivary glands, especially the parotid gland, actively uptake dietary nitrate and secrete it into saliva. Here, we investigated the effect of dietary nitrate on the prevention and treatment of IR-induced parotid gland hypofunction in miniature pigs, and elucidated the underlying mechanism in human parotid gland cells (hPGCs). We found that nitrate administration prevented IR-induced parotid gland damage in a dose-dependent manner, by maintaining the function of irradiated parotid gland tissue. Nitrate could increase sialin expression, a nitrate transporter expressed in the parotid gland, making the nitrate-sialin feedback loop that facilitates nitrate influx into cells for maintaining cell proliferation and inhibiting apoptosis. Furthermore, nitrate enhanced cell proliferation via the epidermal growth factor receptor (EGFR)-protein kinase B (AKT)-mitogen-activated protein kinase (MAPK) signaling pathway in irradiated parotid gland tissue. Collectively, nitrate effectively prevented IR-induced xerostomia via the EGFR–AKT-MAPK signaling pathway. Dietary nitrate supplementation may provide a novel, safe, and effective way to resolve IR-induce xerostomia.
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for: Figure 1G, Figure 2E, Figure 3A-D, and Figure 6 A,C,D and E, available on Dryad Digital Repository (doi:10.5061/dryad.fn2z34ttq).
Dietary nitrate supplementation prevents radiotherapy-induced xerostomiaDryad Digital Repository, doi:10.5061/dryad.fn2z34ttq.
- Songlin Wang
- Songlin Wang
- Songlin Wang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: Animal studies were conducted according to the NIH's Guide for the Care and Use of Laboratory Animals, and approved by the Animal Care and Use Committee of Capital Medical University
Human subjects: Human parotid gland biopsy sample was obtained under a protocol approved by the ethics committee of Beijing Stomatological Hospital, Capital Medical University
- Wafik S El-Deiry, Brown University, United States
© 2021, Feng et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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