[Research Articles] Platelet-derived growth factor C signaling is a potential therapeutic target for radiation proctopathy

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.

Source: Science Translational Medicine - February 24, 2021 Category: Biomedical Science Authors: Lu, W., Xie, Y., Huang, B., Ma, T., Wang, H., Deng, B., Zou, S., Wang, W., Tang, Q., Yang, Z., Li, X., Wang, L., Fang, L. Tags: Research Articles Source Type: research