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29 March 2019 Low-Dose Radiation Promotes the Proliferation and Migration of AGE-Treated Endothelial Progenitor Cells Derived from Bone Marrow via Activating SDF-1/CXCR4/ERK Signaling Pathway
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Abstract

Low-dose radiation (LDR) has been confirmed to mobilize bone marrow-derived endothelial progenitor cells (EPCs) and promote diabetic wound healing. But it is unclear whether LDR acts directly on EPCs and promotes their proliferation and migration. Given the key role of advanced glycosylation end products (AGE) in the pathogenesis of diabetes, we used AGE to induce EPC damage. We then investigated the effect of LDR on the proliferation and migration of AGE-treated EPCs and explored the underlying mechanisms. EPCs cultured in vitro were treated with different concentrations of AGE, and the cells were then exposed to different low doses and treated with a specific antagonist for CXCR4, AMD3100 (1 lmol/l). The proliferation and migration abilities of EPCs were detected using the CCK-8 and wound healing assays, respectively. The mRNA and protein expression of SDF-1 and CXCR4 in AGE-treated EPCs were measured using qPCR and Western blot analysis, respectively. The expressions of ERK and phosphorylated ERK (pERK) were detected using Western blot analysis. The results showed that 200 mg/l and 400 mg/l AGE had an inhibitory effect on the proliferation of EPCs, and this inhibitory effect was exerted in a dose- and time-dependent manner. AGE significantly reduced the migration ability of EPCs cultured in vitro. After the cells received either 50 or 75 mGy low-dose irradiation, the proliferation of EPCs and AGE-treated EPCs was clearly increased; in addition, LDR also enhanced cell migration ability, but this enhancement was counteracted by AMD3100. Results from qPCR and Western blot analysis showed that LDR increased the mRNA and protein expression of SDF-1/ CXCR4. LDR also upregulated pERK expression in EPCs and AGE-treated EPCs, but LDR-induced upregulation of pERK expression was inhibited by AMD3100. These findings indicate that LDR can directly activate the SDF-1/CXCR4 biological axis and downstream ERK signaling pathway, and promote the proliferation and migration abilities of EPCs by increasing the expression of SDF-1, CXCR4 and pERK in EPCs.

©2019 by Radiation Research Society. All rights of reproduction in any form reserved.
Ping Wang, Haifeng Zhang, Zhuo Li, Xiaobo Liu, Yingli Jin, Manman Lei, Zixuan Jiao, Yaru Bi, and Weiying Guo "Low-Dose Radiation Promotes the Proliferation and Migration of AGE-Treated Endothelial Progenitor Cells Derived from Bone Marrow via Activating SDF-1/CXCR4/ERK Signaling Pathway," Radiation Research 191(6), 518-526, (29 March 2019). https://doi.org/10.1667/RR15200.1
Received: 6 August 2018; Accepted: 1 March 2019; Published: 29 March 2019
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