PrP(c) deficiency and dasatinib protect mouse intestines against radiation injury by inhibiting of c-Src.

Details

Serval ID
serval:BIB_1646BF5BEE4F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
PrP(c) deficiency and dasatinib protect mouse intestines against radiation injury by inhibiting of c-Src.
Journal
Radiotherapy and Oncology : Journal of the European Society For Therapeutic Radiology and Oncology
Author(s)
Strup-Perrot C., Vozenin M.C., Monceau V., Pouzoulet F., Petit B., Holler V., Perrot S., Desquibert L., Fouquet S., Souquere S., Pierron G., Rousset M., Thenet S., Cardot P., Benderitter M., Deutsch E., Aigueperse J.
ISSN
1879-0887 (Electronic)
ISSN-L
0167-8140
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
120
Number
1
Pages
175-183
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
BACKGROUND & AIM: Despite extensive study of the contribution of cell death and apoptosis to radiation-induced acute intestinal injury, our knowledge of the signaling mechanisms involved in epithelial barrier dysfunction remains inadequate. Because PrP(c) plays a key role in intestinal homeostasis by renewing epithelia, we sought to study its role in epithelial barrier function after irradiation.
DESIGN: Histology, morphometry and plasma FD-4 levels were used to examine ileal architecture, wound healing, and intestinal leakage in PrP(c)-deficient (KO) and wild-type (WT) mice after total-body irradiation. Impairment of the PrP(c) Src pathway after irradiation was explored by immunofluorescence and confocal microscopy, with Caco-2/Tc7 cells. Lastly, dasatinib treatment was used to switch off the Src pathway in vitro and in vivo.
RESULTS: The decrease in radiation-induced lethality, improved intestinal wound healing, and reduced intestinal leakage promoted by PrP(c) deficiency demonstrate its involvement in acute intestinal damage. Irradiation of Cacao2/Tc7 cells induced PrP(c) to target the nuclei associated with Src activation. Finally, the protective effect triggered by dasatinib confirmed Src involvement in radiation-induced acute intestinal toxicity.
CONCLUSION: Our data are the first to show a role for the PrP(c)-Src pathway in acute intestinal response to radiation injury and offer a novel therapeutic opportunity.
Pubmed
Web of science
Create date
07/10/2016 9:08
Last modification date
20/08/2019 12:45
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