血小板源性生长因子受体
癌症研究
趋化因子
促炎细胞因子
转录因子
纤维化
生长因子
血小板衍生生长因子
受体
医学
炎症
药理学
生物
免疫学
内科学
基因
生物化学
作者
Weisi Lu,Yunling Xie,Binjie Huang,Tenghui Ma,Huaiming Wang,Boxiong Deng,Shaomin Zou,Wencong Wang,Qin Tang,Ziqing Yang,Xuri Li,Lei Wang,Lekun Fang
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2021-02-24
卷期号:13 (582)
被引量:8
标识
DOI:10.1126/scitranslmed.abc2344
摘要
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.
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