Molecular Determinants of Vertebrate Vasculature and Development

脊椎动物脉管系统和发育的分子决定因素

• 批准号: RGPIN-2017-04787
• 负责人: Majumder, Mousumi
• 金额: $ 1.89万
• 依托单位: Brandon University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=745798
• 关键词: Molecular; Determinants; Vertebrate; Vasculature; Development

Background: Vertebrate vascular system is vital for blood circulation, gas miRNA functions; we shall stimulate miRNA in HUVEC cells with EP4 agonist and inhibit miRNA functions in HUVEC-miR cells with EP4 antagonist. Functional dependence on EP4 mediated signaling (PI3K/AKT, ERK phosphorylation) will establish the link between miRNAs and EP4.Objective 3: (a) To study the role of the PGE2 in embryonic development and vasculogenesis in Zebrafish model; we shall inject PGE2 in fish embryo in a dose-dependent way and record developmental changes. We shall conduct microarrays with embryo extracts to identify miRNA changes. (b) To test miRNA functions, we shall knock down miRNAs in Zebrafish embryo and measure growth change. This pilot study will identify novel miRNAs regulated by PGE2 during vasculogenesis.Objective 4: To find gene expression changes due to PGE2 treatment in Zebrafish; we shall conduct microarrays in Vehicle and PGE2 treated fish embryo extracted mRNA to identify novel genes might involve in vertebrate development.Significance: With various approaches, this program will, therefore, add new determinants in the catalog of vertebrate development. Identification of the physiological roles of PGE2 and miRNA in vasculogenesis; EP4 signaling regulating miRNA functions, this program will, therefore, modify the course of currently used drugs targeting EP4.

背景资料：脊椎动物血管系统对血液循环至关重要，因此我们将用EP 4激动剂刺激HUVEC细胞中的miRNA，并用EP 4拮抗剂抑制HUVEC-miR细胞中的miRNA功能。通过对EP 4介导的信号（PI 3 K/AKT，ERK磷酸化）的功能依赖性研究，将建立miRNA与EP 4之间的联系。目的3：（a）研究PGE 2在斑马鱼胚胎发育和血管发生中的作用。我们将使用胚胎提取物进行微阵列以鉴定miRNA的变化。(b)为了测试miRNA的功能，我们将敲除斑马鱼胚胎中的miRNA并测量生长变化。目的4：研究PGE 2处理对斑马鱼基因表达的影响，并利用微阵列技术对PGE 2处理的斑马鱼胚胎mRNA进行分析，以筛选出可能参与脊椎动物发育的新基因。意义：通过多种方法，本研究将为脊椎动物发育的研究增加新的决定因素。鉴定PGE 2和miRNA在血管发生中的生理作用; EP 4信号调节miRNA功能，因此，该计划将修改目前使用的靶向EP 4的药物的过程。