重组瘦素通过PI3K/Akt/mTOR/S6激酶信号通路诱导血管生成诱导VEGF A合成的可能机制:基于鸡绒毛膜尿囊膜模型的分析

IF 1.8 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE
Journal of Vascular Research Pub Date : 2021-01-01 Epub Date: 2021-06-24 DOI:10.1159/000516498
Reji Manjunathan, Nalini Devarajan, Malathi Ragunathan
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引用次数: 12

摘要

本研究旨在通过PI3K/Akt/mTOR/S6激酶参与的信号通路,实现人重组瘦素在合成VEGF A的同时诱导新生血管的能力。方法:用重组人瘦素和特异性信号分子(雷帕霉素和wortmannin)抑制剂孵育鸡绒毛膜(CAM),检测PI3K/Akt/mTOR/S6激酶通路参与瘦素诱导的VEGF A合成。在多种方法的支持下,我们详细分析了特定信号分子在重组瘦素诱导的通过VEGF A合成的生理性血管生成中的作用。结果:在抑制剂的存在下,人重组瘦素合成VEGF A的能力明显减弱。这一观察结果支持PI3K/Akt/mTOR/S6激酶信号分子在人重组瘦素介导的VEGF A合成中发挥作用,同时诱导CAM血管生成。结论:人重组瘦素通过激活PI3K/Akt/mTOR/S6激酶信号通路合成VEGF A并诱导新生血管生长,反映了人重组瘦素在治疗中的应用机制。这些数据也表明在生理环境下mTOR和S6激酶分子在血管生成中的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Possible Mechanism of Human Recombinant Leptin-Induced VEGF A Synthesis via PI3K/Akt/mTOR/S6 Kinase Signaling Pathway while Inducing Angiogenesis: An Analysis Using Chicken Chorioallantoic Membrane Model.

Introduction: The present study aimed to realize human recombinant leptin 's ability to synthesize VEGF A while inducing neovascularization through PI3K/Akt/mTOR/S6 kinase involved signaling pathway.

Methods: To examine the PI3K/Akt/mTOR/S6 kinase pathway involvement in leptin-induced VEGF A synthesis, the chick chorioallantoic membrane (CAM) was incubated with human recombinant leptin and specific inhibitors of the proposed signaling molecules (rapamycin and wortmannin). We analyzed the role of specified signaling molecules in human recombinant leptin-induced physiological angiogenesis via VEGF A synthesis in detail with the support of various methodologies.

Results: Human recombinant leptin's ability to synthesize VEGF A is diminished significantly in the presence of inhibitors. This observation supported the role of PI3K/Akt/mTOR/S6 kinase signaling molecules in human recombinant leptin-mediated VEGF A synthesis while inducing angiogenesis in CAM.

Conclusion: Synthesis of VEGF A, followed by the growth of new blood vessels, by human recombinant leptin via the activation of the PI3K/Akt/mTOR/S6 kinase signaling pathway reflects mechanistic therapeutic application of human recombinant leptin. The data also signify the role of mTOR and S6 kinase molecules in angiogenesis under a physiological environment.

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来源期刊
Journal of Vascular Research
Journal of Vascular Research 医学-生理学
CiteScore
3.40
自引率
0.00%
发文量
25
审稿时长
>12 weeks
期刊介绍: The ''Journal of Vascular Research'' publishes original articles and reviews of scientific excellence in vascular and microvascular biology, physiology and pathophysiology. The scope of the journal covers a broad spectrum of vascular and lymphatic research, including vascular structure, vascular function, haemodynamics, mechanics, cell signalling, intercellular communication, growth and differentiation. JVR''s ''Vascular Update'' series regularly presents state-of-the-art reviews on hot topics in vascular biology. Manuscript processing times are, consistent with stringent review, kept as short as possible due to electronic submission. All articles are published online first, ensuring rapid publication. The ''Journal of Vascular Research'' is the official journal of the European Society for Microcirculation. A biennial prize is awarded to the authors of the best paper published in the journal over the previous two years, thus encouraging young scientists working in the exciting field of vascular biology to publish their findings.
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