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A hepatocyte growth factor/MET-induced antiapoptotic pathway protects against radiation-induced salivary gland dysfunction

Authors
 Yeo Jun Yoon  ;  Hyun-Soo Shin  ;  Jae-Yol Lim 
Citation
 RADIOTHERAPY AND ONCOLOGY, Vol.138 : 9-16, 2019 
Journal Title
 RADIOTHERAPY AND ONCOLOGY 
ISSN
 0167-8140 
Issue Date
2019
Keywords
Hepatocyte growth factor ; Radiation ;  Salivary gland ; Three-dimensional cell culture
Abstract
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.
Files in This Item:
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DOI
10.1016/j.radonc.2019.05.012
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Lim, Jae Yol(임재열) ORCID logo https://orcid.org/0000-0002-9757-6414
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/170396
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