期刊
RADIOTHERAPY AND ONCOLOGY
卷 138, 期 -, 页码 9-16出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.radonc.2019.05.012
关键词
Salivary gland; Radiation; Three-dimensional cell culture; Hepatocyte growth factor
资金
- National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [NRF-2017M3A9B4032053]
- NRF - Ministry of Science and ICT, Republic of Korea [NRF-2018R1A2B3004269]
Objective: Hepatocyte growth factor (HGF) and its receptor MET are expressed in the salivary glands during developmental stages and tumor formation; however, the function of HGF in injured salivary gland tissues remains unclear. The present study investigated the role of HGF in protecting the salivary glands against radiation-induced injury using an organotypic culture method. Materials and methods: Acinar-like organoids were formed by means of a three-dimensional (3D) human parotid tissue-derived spheroids (hPTS) culture method. Radioprotective effects of HGF on irradiated hPTS and signaling pathways on radioprotection were investigated. Results: We detected MET expression in hPTS grown in a 3D culture. Treatment of irradiated hPTS with recombinant human HGF (rhHGF) restored salivary marker expression and secretory function of hPTS. Changes in the phosphorylation levels of apoptosis-related proteins through HGF-MET axis inhibited radiation-induced apoptosis. Treatment with PHA665752, a MET inhibitor, blocked MET-PI3K-AKT pathway, increased apoptosis, and suppressed the radioprotective effect of rhHGF against IR-induced damage of hPTS. Conclusions: These results suggest that HGF is a key effector of radioprotection and that HGF-MET-PI3K-AKT axis is involved in protecting the salivary glands from radiation-induced apoptosis. (C) 2019 The Authors. Published by Elsevier B.V.
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