曲匹鲁汀的抗血管生成作用是通过抑制人血管内皮细胞中阿皮素启动子活性和缩短 mRNA 半衰期来介导的。
The anti-angiogenic effect of tryptanthrin is mediated by the inhibition of apelin promoter activity and shortened mRNA half-life in human vascular endothelial cells.
机构信息
Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan, ROC; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Taoyuan, Taiwan, ROC.
Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan, ROC; Program in Molecular Medicine, School of Life Sciences, National Yang Ming University, Taipei, Taiwan, ROC.
出版信息
Phytomedicine. 2019 May;58:152879. doi: 10.1016/j.phymed.2019.152879. Epub 2019 Feb 26.
BACKGROUND
Anti-angiogenesis is an important strategy of psoriasis treatment, but the side effects of systemic agents remain difficult to overcome. Topical use of indigo naturalis ointment has been proved to improve the skin lesion of psoriasis effectively and safely and one of its major components, tryptanthrin, has been demonstrated to have anti-angiogenic effect. Apelin, which has been reported to act as an angiogenic factor that could stimulate the proliferation and migration of vascular endothelial cells and proved to be elevated in psoriasis patients, is a potential target of anti-angiogenic therapy.
PURPOSE
We aim to find out if tryptanthrin works on the apelin pathway and study its anti-angiogenic mechanism.
STUDY DESIGN
Human umbilical vein endothelial cells (HUVECs) were used as the in vitro model.
METHODS
The effect of tryptanthrin on the expression of apelin and its receptor, APJ, was examined. The mRNA stability, promoter activity, and bioactivity of apelin, were also investigated. Migration and tube formation assay were used to evaluate the relationship between tryptanthrin and apelin. PD98059 and wortmannin were used to study the role of ERK1/2 MAPK and PI3K in apelin signaling pathway.
RESULTS
We demonstrated that tryptanthrin could inhibit the expression of apelin, attenuated the stability of apelin mRNA, and significantly inhibited the apelin promoter activity. The addition of apelin-13 restored the suppression of tube formation and migration by tryptanthrin. Both PD98059 and wortmannin could down-regulate the apelin mRNA expression suggesting the important signaling role of ERK1/2 MAPK and PI3K in the gene expression of apelin.
CONCLUSION
The anti-angiogenic effect of tryptanthrin was mediated by down-regulating apelin gene expression through suppression of promoter activity and decrease of mRNA stability in human vascular endothelial cells.
背景
抗血管生成是治疗银屑病的重要策略，但系统药物的副作用仍然难以克服。局部使用靛蓝天然软膏已被证明能有效且安全地改善银屑病的皮肤病变，其主要成分之一色胺酮已被证明具有抗血管生成作用。Apelin 已被报道作为一种血管生成因子，可刺激血管内皮细胞的增殖和迁移，并且已被证明在银屑病患者中升高，是抗血管生成治疗的潜在靶点。
目的
我们旨在研究色胺酮是否作用于 Apelin 通路，并研究其抗血管生成机制。
研究设计
人脐静脉内皮细胞（HUVEC）用作体外模型。
方法
研究色胺酮对 Apelin 及其受体 APJ 的表达的影响。还研究了 Apelin 的 mRNA 稳定性、启动子活性和生物活性。迁移和管形成测定用于评估色胺酮与 Apelin 之间的关系。使用 PD98059 和 Wortmannin 研究 ERK1/2 MAPK 和 PI3K 在 Apelin 信号通路中的作用。
结果
我们证明色胺酮可以抑制 Apelin 的表达，减弱 Apelin mRNA 的稳定性，并显著抑制 Apelin 启动子活性。添加 Apelin-13 可恢复色胺酮对管形成和迁移的抑制作用。PD98059 和 Wortmannin 均可下调 Apelin mRNA 表达，表明 ERK1/2 MAPK 和 PI3K 在 Apelin 基因表达中具有重要的信号作用。
结论
色胺酮的抗血管生成作用是通过抑制人血管内皮细胞中启动子活性和降低 mRNA 稳定性来下调 Apelin 基因表达介导的。
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