Platelet-derived growth factor-BB promotes proliferation and migration of retinal microvascular pericytes by up-regulating the expression of C-X-C chemokine receptor types 4
Platelet-derived growth factor-BB promotes proliferation and migration of retinal microvascular pericytes by up-regulating the expression of C-X-C chemokine receptor types 4
复制标题
血小板源性生长因子-BB通过上调C-X-C趋化因子受体4型表达促进视网膜微血管周细胞增殖和迁移
DOI：
10.3892/etm.2019.8016
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发表时间：
2019
影响因子：
2.7
通讯作者：
Yuanzhi Yuan
中科院分区：
文献类型：
--
作者：
Dan;Yi;Jing Wang;Xi Zhang;Jing;R. Zou;Yuanzhi Yuan
基质细胞衍生生长因子-1α是C-X-C趋化因子受体4和7的配体，参与脉络膜新生血管的形成。以往的研究表明，在肿瘤新生血管形成过程中，通过增加周细胞的募集，血小板衍生生长因子-BB/血小板衍生生长因子受体-β和SDF-1α/CXCR4轴之间存在串扰。然而，这两个信号通路之间的相互作用在视网膜微血管周细胞中的作用仍然知之甚少。用Western blotting和逆转录定量聚合酶链式反应检测周细胞中CXCR4和CXCR7的表达，用细胞计数试剂盒8和Transwell迁移试验检测经SDF1α处理的周细胞的存活和迁移情况。外源性PDGF-BB通过PDGFR-β增强CXCR4和CXCR7的表达，并呈剂量和时间依赖性。此外，血小板衍生生长因子BB可增加SDF-1α处理的周细胞的存活率和迁移能力，该作用可分别被CXCR4和STAT3的抑制剂AMD3100和氯硝柳胺抑制。PDGFBB/PDGFFR-β和SDF1JAK2/α/CXCR4/CXCR7之间的串扰参与了JAK2/STAT3信号通路。血小板衍生生长因子BB可上调CXCR4、CXCR7和PDGFR-β的表达，其机制可能与信号转导通路信号转导通路3的磷酸化有关。小干扰RNA-PDGFR-β表达下调周细胞中CXCR4和CXCR7的表达。因此，血小板衍生生长因子-BB直接靶向β，在调节CXCR4和CXCR7的表达中发挥重要作用，最终影响经α处理的周细胞的存活和迁移。因此，靶向CXCR4/CXCR7可能成为一种潜在的眼底疾病治疗策略。
Stromal cell-derived growth factor (SDF)-1α acts as a ligand to C-X-C chemokine receptors 4 (CXCR4) and 7 (CXCR7), which are involved in the formation of choroidal neovascularization. Previous studies have demonstrated crosstalk between the platelet-derived growth factor (PDGF)-BB/PDGF receptor (PDGFR)-β and SDF-1α/CXCR4 axes during tumor neovascularization by increasing the recruitment of pericytes. However, the effects of interactions between these two signaling pathways in retinal microvascular pericytes remain poorly understood. Western blotting and reverse transcription-quantitative PCR were used to measure CXCR4 and CXCR7 expression in PDGF-BB-treated pericytes, whilst Cell Counting Kit-8 and Transwell migration assays were used to investigate cell viability and migration following PDGF-BB pretreatment on SDF-1α-treated pericytes. Exogenous PDGF-BB enhanced CXCR4 and CXCR7 expression through PDGFR-β in a dose- and time-dependent manners. In addition, PDGF-BB increased cell viability and migration in SDF-1α-treated pericytes, which were inhibited by AMD3100 and niclosamide, inhibitors for CXCR4 and STAT3 respectively. Crosstalk between PDGF-BB/PDGFR-β and SDF-1α/CXCR4/CXCR7 were involved in the JAK2/STAT3 signaling pathway. PDGF-BB treatment enhanced CXCR4, CXCR7 and PDGFR-βexpression, which may be associated with the phosphorylation of STAT3. siRNA-PDGFR-β transfection reduced CXCR4 and CXCR7 expression in pericytes. Therefore, PDGF-BB directly targets PDGFR-β and serves an important role in regulating CXCR4 and CXCR7 expression, ultimately affecting viability and migration in SDF-1α-treated pericytes. Therefore, targeting CXCR4/CXCR7 may serve as a potential therapeutic strategy for fundus diseases.