In:
Science Translational Medicine, American Association for the Advancement of Science (AAAS), Vol. 13, No. 582 ( 2021-02-24)
Kurzfassung:
Radiation proctopathy (RP) is characterized by inflammation of colorectal tissue and is a common complication of radiation therapy for pelvic malignancies with high incidence but lacking effective treatment. Here, we found that platelet-derived growth factor C (PDGF-C) and fibrosis markers were up-regulated in tissue samples from patients with RP and in rectal tissues after irradiation in a mouse model of RP. Genetic deletion of Pdgf-c in mice ameliorated RP-induced injuries. Genome-wide gene expression profiling and in vitro assays revealed that the promotive effect of PDGF-C in RP development was mediated by activation of PDGF receptors (PDGFRs) and C-X-C motif chemokine receptor 4, a proinflammatory chemokine regulated by transcription factor ETS variant transcription factor 1. Treatment with crenolanib, a selective inhibitor of PDGFRs, prevented or reduced RP in mice after irradiation. These results reveal that inhibition of PDGF-C signaling may have therapeutic value for the treatment of RP.
Materialart:
Online-Ressource
ISSN:
1946-6234
,
1946-6242
DOI:
10.1126/scitranslmed.abc2344
Sprache:
Englisch
Verlag:
American Association for the Advancement of Science (AAAS)
Publikationsdatum:
2021