Panax notoginseng saponins promote endothelial progenitor cell angiogenesis via the Wnt/β-catenin pathway.

Panax notoginseng saponins promote endothelial progenitor cell angiogenesis via the Wnt/β-catenin pathway.
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三七皂苷通过 Wntβ-连环蛋白途径促进内皮祖细胞血管生成

DOI:
10.1186/s12906-021-03219-z
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发表时间:
2021-02-08
影响因子:
3.9
通讯作者:
Zhou N
Zhou N
中科院分区:
医学3区
文献类型:
--
作者:
Zhu P;Jiang W;He S;Zhang T;Liao F;Liu D;An X;Huang X;Zhou N

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牵张成骨术是颅颌面外科的一种有效治疗方法。然而,再生组织处的足够血液供应的问题限制了其广泛应用。三七总皂苷(PNS)是一种传统中药,常用于治疗一系列血管生成性疾病。然而,三七总皂苷改变内皮祖细胞(EPCs)血管生成的机制尚未阐明。通过免疫荧光鉴定EPC,通过其对荧光标记的Dil-ac-LDL和FITC-UEA-1的摄取来证实。用不同浓度的三七总皂苷处理内皮祖细胞,在确定最佳浓度的基础上,观察三七总皂苷对内皮祖细胞增殖的影响。观察三七总皂苷对血管生成和迁移、血管生成细胞因子mRNA表达及Wnt通路蛋白的影响。敲除EPCs中β-catenin后,用最佳浓度的三七总皂苷处理EPCs,通过微管形成和迁移实验评价其血管生成能力。此外,然后通过WB和RT-qPCR评估与血管生成和Wnt/β-连环蛋白相关的细胞因子的表达。我们能够确定PNS促进细胞增殖、管形成和迁移的最佳浓度为6.25 mg/L。PNS治疗增加了VEGF、bFGF、VE-钙粘蛋白、WNT 3a、LRP 5、β-连环蛋白和TCF 4的mRNA水平。在敲低β-catenin表达后,我们发现PNS足以部分逆转EPC血管生成的抑制。6.25 mg/L三七总皂苷可通过激活Wnt/β-catenin信号通路促进EPC血管生成。
Distraction osteogenesis (DO) is an effective treatment in craniomaxillofacial surgery. However, the issue of sufficient blood supply at the regeneration tissue has limited its wide application. Panax notoginseng saponins (PNS) is a Traditional Chinese Medicine that is commonly used to treat a range of angiogenic diseases. However, the mechanisms whereby PNS alters angiogenesis in endothelial progenitor cells (EPCs) have yet to be clarified. EPCs were identified by immunofluorescence, confirmed by their uptake of fluorescently labeled Dil-ac-LDL and FITC-UEA-1. EPCs were treated with different concentrations of PNS, and the effects of PNS on cell proliferation were measured on the optimal concentration of PNS determined. The effects of PNS on angiogenesis and migration, angiogenic cytokines mRNA expression and the proteins of the Wnt pathway were investigated. Then knocked down β-catenin in EPCs and treated with the optimum concentrational PNS, their angiogenic potential was evaluated in tube formation and migration assays. In addition, the expression of cytokines associated with angiogenesis and Wnt/β-catenin was then assessed via WB and RT-qPCR. We were able to determine the optimal concentration of PNS in the promotion of cell proliferation, tube formation, and migration to be 6.25 mg/L. PNS treatment increased the mRNA levels of VEGF, bFGF, VE-Cadherin, WNT3a, LRP5, β-catenin, and TCF4. After knocked down β-catenin expression, we found that PNS could sufficient to partially reverse the suppression of EPC angiogenesis. Overall, 6.25 mg/L PNS can promote EPC angiogenesis via Wnt/β-catenin signaling pathway activation.
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