A hepatocyte growth factor/MET-induced antiapoptotic pathway protects against radiation-induced salivary gland dysfunction.
Radiother Oncol
; 138: 9-16, 2019 09.
Article
en En
| MEDLINE
| ID: mdl-31136962
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 ANDMETHODS:
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.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Traumatismos por Radiación
/
Glándulas Salivales
/
Factor de Crecimiento de Hepatocito
/
Apoptosis
/
Proteínas Proto-Oncogénicas c-met
Límite:
Humans
Idioma:
En
Revista:
Radiother Oncol
Año:
2019
Tipo del documento:
Article