蛋白酶激活受体2经RhoA信号抑制人内皮祖细胞增殖、迁移功能
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南京医科大学第一附属医院

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R562.25

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PM2.5上调非编码区增强子Enh1元件功能经由SPDEF信号加剧哮喘气道上 皮细胞重构的机制研究


Protease-activated receptor-2 inhibits human endothelial progenitor cells proliferation and migration via RhoA signaling
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The molecular mechanism of PM2.5-induced SPDEF signal regulation by enhancer Enh1 in airway epithelial cell remodeling in asthma

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    摘要:

    目的:探究蛋白酶激活受体2(protease-activated receptor 2,PAR2)对人内皮祖细胞(endothelial progenitor cells,EPCs)功能的影响。方法:EPCs予以PAR2天然激动剂类胰蛋白酶、合成激动剂SLIGKV-NH2、合成抑制剂FSLLRY-NH2处理,EdU、Transwell实验观察EPCs增殖、迁移,qPCR、ELISA分析检测相关细胞因子及受体表达,免疫印迹法评估RhoA水平;同时给予RhoA特异性抑制剂Y-27632,观察PAR2活化效应可否被取消。结果:PAR2激动剂可剂量依赖性抑制EPCs增殖及迁移(P<0.05),下调VEGF-A、VEGFR-2、SDF-1及CXCR-4等表达(P<0.05),该效应可被PAR2抑制剂取消;活化PAR2可显著上调EPCs RhoA表达(P<0.05),抑制PAR2活性可取消该效应;Y-27632可逆转PAR2激动剂导致的EPCs细胞增殖、迁移抑制(P<0.05)。结论:PAR2经RhoA信号抑制EPCs增殖、迁移功能,是极具潜力的内皮再生与血管生成调控靶点。

    Abstract:

    Objective: The present study aims to investigate the role of protease-activated receptor 2 (PAR2) in the regulation of human endothelial progenitor cells (EPCs) function. Methods: EPCs were stimulated with tryptase (a natural agonist of PAR2), SLIGKV-NH2 (a synthetic agonist of PAR2) and FSLLRY-NH2 (an antagonist of PAR2). Cell proliferation and migration were evaluated by EdU incorporation and Transwell model. Expression of the cytokines and receptors were estimated by qPCR and ELISA. Level of intercellular RhoA was assessed by western blot analysis. And RhoA antagonist Y-27632 was also applied to determine whether the effects of PAR2 activation can be abolished by RhoA inhibition. Results: The agonists of PAR2 dramatically inhibited EPCs proliferation and migration in a dose-dependent manner (P<0.05). PAR2 activation markedly suppressed the expression of VEGF-A, VEGFR-2, SDF-1 and CXCR4 (P<0.05). All these effects can be abolished by the PAR2 antagonist (P<0.05). And PAR2 activation increased the level of RhoA in EPCs, which was also repressed by FS (P<0.05). Y-27632 notably reversed the influence of PAR2 activation on EPCs proliferation and migration (P<0.05). Conclusion: Activation of PAR2 blunted EPCs proliferation and migration via RhoA signal, hinting a potential role of PAR2 as a novel target for the modulation of endothelial regeneration and vasculogenesis.

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  • 收稿日期:2022-12-13
  • 最后修改日期:2023-02-02
  • 录用日期:2023-05-10
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