The role of endocannabinoid receptors in regulating trophoblast cell function

内源性大麻素受体在调节滋养层细胞功能中的作用

基本信息

  • 批准号:
    RGPIN-2019-07101
  • 负责人:
  • 金额:
    $ 2.04万
  • 依托单位:
  • 依托单位国家:
    加拿大
  • 项目类别:
    Discovery Grants Program - Individual
  • 财政年份:
    2019
  • 资助国家:
    加拿大
  • 起止时间:
    2019-01-01 至 2020-12-31
  • 项目状态:
    已结题

项目摘要

BACKGROUND***Endogenous cannabinoids are lipid-based signaling molecules which regulate pain, appetite, neuroendocrine function. Recently it has been reported that cannabinoid receptors 1 and 2 (CB1and CB2), along with a third subtype, GPR55, may be linked to endocannabinoid signaling in reproductive tissues. They may contribute to the development of the placenta and the function of trophoblast cells (the stem cells which comprise the placenta). However, the specific roles and the mechanisms by which these receptors regulate the primary interface that governs maternal/fetal interactions are poorly understood. In vitro evidence from my laboratory suggests that stimulation of the CB1 receptor in cultured trophoblast cells substantially reduce their ability to invade and form a fused syncytium; essential steps in forming the maternal-fetal interface. ******HYPOTHESIS***Our hypothesis is that disruption of cannabinoid receptor signaling in trophoblast cells will result in altered progression of the processes associated with placental development; invasion, vascular remodeling and endocrine function.******RESEARCH PROGRAM***Aim 1. Elucidation of the functional pathways impacted by cannabinoid receptor signaling in cultured human trophoblasts. Mechanistic studies will be conducted using human trophoblast cells since there are no universally accepted rodent trophoblast cell lines. We will evaluate the impact of activating and inhibiting CB1, CB2 and GPR55 with receptor specific agonists and antagonists in trophoblast cell lines. Trophoblast functional outcomes such as invasion, syncytium formation and endocrine signaling (hormone production) will be monitored. We will confirm our observations using isolated human primary trophoblasts.******Aim 2. The role of mitochondria in endocannabinoid signaling. We will determine the contribution of mitochondrial free radical production and changes in organellar morphology towards cannabinoid receptor signaling by disrupting these process with various pharmacological and molecular approaches and evaluate the consequences on trophoblast function (Aim 1). ******Aim 3. Consequences of systemic disruption of endocannabinoid receptor signaling on trophoblast function and placentation. We will evaluate the consequence of disrupting each of the three cannabinoid receptor signaling pathways, currently associated reproductive outcomes, on the progression of placentation at two time points during gestation. We will evaluate changes in trophoblast invasion and vascular remodeling; two processes which are critical to placentation. We will associate these outcomes with fetal growth.******TRAINING OF HQP***My program facilitates the training of graduate, undergraduate students using an integrated approach to technical training and knowledge translation. My commitment to training HQP extends beyond my laboratory as I have developed a pan-university outreach program which facilitates undergraduate and graduate student training in science communication.**
内源性大麻素是一种以脂质为基础的信号分子,可调节疼痛、食欲和神经内分泌功能。最近有报道称,大麻素受体1和2 (cb1和CB2)以及第三种亚型GPR55可能与生殖组织中的内源性大麻素信号传导有关。它们可能有助于胎盘的发育和滋养细胞(构成胎盘的干细胞)的功能。然而,这些受体调节母体/胎儿相互作用的主要界面的具体作用和机制尚不清楚。来自我实验室的体外证据表明,刺激培养的滋养细胞中的CB1受体大大降低了它们入侵和形成融合合胞体的能力;形成母胎界面的基本步骤。******假设***我们的假设是,滋养细胞中大麻素受体信号的破坏将导致胎盘发育相关过程的改变;侵袭、血管重塑与内分泌功能。******研究计划***目的大麻素受体信号通路对培养的人滋养细胞功能通路的影响。由于没有普遍接受的啮齿动物滋养细胞系,因此将使用人类滋养细胞进行机制研究。我们将评估受体特异性激动剂和拮抗剂在滋养细胞系中激活和抑制CB1、CB2和GPR55的影响。将监测滋养细胞的功能结果,如侵袭、合胞体形成和内分泌信号(激素产生)。我们将用分离的人类初级滋养细胞来证实我们的观察结果。* * * * * *的目标2。线粒体在内源性大麻素信号传导中的作用。我们将通过各种药理学和分子方法破坏这些过程,确定线粒体自由基产生和细胞器形态变化对大麻素受体信号传导的贡献,并评估对滋养细胞功能的影响(目的1)。******目的3。内源性大麻素受体信号全身性破坏对滋养细胞功能和胎盘的影响。我们将评估破坏三种大麻素受体信号通路的后果,目前相关的生殖结果,在妊娠期间的两个时间点对胎盘的进展。我们将评估滋养细胞侵袭和血管重塑的变化;这两个过程对胎盘发育至关重要。我们将把这些结果与胎儿生长联系起来。****** HQP培训***我的项目通过技术培训和知识转化的综合方法促进了研究生和本科生的培训。我对培养HQP的承诺超出了我的实验室,因为我已经制定了一个泛大学的外展计划,以促进本科生和研究生在科学传播方面的培训

项目成果

期刊论文数量(0)
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会议论文数量(0)
专利数量(0)

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Raha, Sandeep其他文献

Increased expression of mitochondrial glycerophosphate dehydrogenase and antioxidant enzymes in prostate cancer cell lines/cancer
  • DOI:
    10.1080/10715760701579314
  • 发表时间:
    2007-01-01
  • 期刊:
  • 影响因子:
    3.3
  • 作者:
    Chowdhury, Subir K. Roy;Raha, Sandeep;Singh, Gurmit
  • 通讯作者:
    Singh, Gurmit
Reactive oxygen species from mitochondria impacts trophoblast fusion and the production of endocrine hormones by syncytiotrophoblasts
  • DOI:
    10.1371/journal.pone.0229332
  • 发表时间:
    2020-02-24
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    Walker, O'Llenecia S.;Ragos, Rehginald;Raha, Sandeep
  • 通讯作者:
    Raha, Sandeep
Effect of Environmental Contaminants on Beta Cell Function
  • DOI:
    10.1177/1091581811405544
  • 发表时间:
    2011-08-01
  • 期刊:
  • 影响因子:
    2.2
  • 作者:
    Makaji, Emilija;Raha, Sandeep;Holloway, Alison C.
  • 通讯作者:
    Holloway, Alison C.
Protocol for the COVID-19 Wellbeing and Stress Study: a longitudinal study of parent distress, biological stress and child biopsychosocial development during the pandemic and beyond.
  • DOI:
    10.1136/bmjopen-2023-071926
  • 发表时间:
    2023-08-14
  • 期刊:
  • 影响因子:
    2.9
  • 作者:
    Khoury, Jennifer E.;Atkinson, Leslie;Jack, Susan;Bennett, Teresa;Raha, Sandeep;Duku, Eric;Gonzalez, Andrea
  • 通讯作者:
    Gonzalez, Andrea
Fetal and neonatal nicotine exposure in Wistar rats causes progressive pancreatic mitochondrial damage and beta cell dysfunction.
Wistar大鼠中的胎儿和新生儿尼古丁暴露会导致进行性胰腺导致线粒体损伤和β细胞功能障碍。
  • DOI:
    10.1371/journal.pone.0003371
  • 发表时间:
    2008
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    Bruin, Jennifer E.;Petre, Maria A.;Raha, Sandeep;Morrison, Katherine M.;Gerstein, Hertzel C.;Holloway, Alison C.
  • 通讯作者:
    Holloway, Alison C.

Raha, Sandeep的其他文献

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{{ truncateString('Raha, Sandeep', 18)}}的其他基金

The role of endocannabinoids receptors in regulating trophoblast cell function
内源性大麻素受体在调节滋养层细胞功能中的作用
  • 批准号:
    RGPIN-2020-06739
  • 财政年份:
    2022
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Discovery Grants Program - Individual
The role of endocannabinoids receptors in regulating trophoblast cell function
内源性大麻素受体在调节滋养层细胞功能中的作用
  • 批准号:
    RGPIN-2020-06739
  • 财政年份:
    2021
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Discovery Grants Program - Individual
The role of endocannabinoids receptors in regulating trophoblast cell function
内源性大麻素受体在调节滋养层细胞功能中的作用
  • 批准号:
    RGPIN-2020-06739
  • 财政年份:
    2020
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Discovery Grants Program - Individual
Placenta on a chip: A humanized platform for testing of pharmaceuticals and environmental chemicals
胎盘芯片:用于测试药物和环境化学品的人性化平台
  • 批准号:
    523792-2018
  • 财政年份:
    2019
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Collaborative Health Research Projects
McMaster Children and Youth University
麦克马斯特儿童与青少年大学
  • 批准号:
    531628-2018
  • 财政年份:
    2018
  • 资助金额:
    $ 2.04万
  • 项目类别:
    PromoScience
Placenta on a chip: A humanized platform for testing of pharmaceuticals and environmental chemicals
胎盘芯片:用于测试药物和环境化学品的人性化平台
  • 批准号:
    523792-2018
  • 财政年份:
    2018
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Collaborative Health Research Projects
McMaster Children and youth University
麦克马斯特儿童与青少年大学
  • 批准号:
    516050-2017
  • 财政年份:
    2017
  • 资助金额:
    $ 2.04万
  • 项目类别:
    PromoScience
Mitochondrial signaling in adipose tissue
脂肪组织中的线粒体信号传导
  • 批准号:
    342032-2009
  • 财政年份:
    2013
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Discovery Grants Program - Individual
Development of a platform for point-of care testing: Accelerating the Assay Pipeline
开发即时检测平台:加速检测流程
  • 批准号:
    461032-2013
  • 财政年份:
    2013
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Engage Grants Program
Mitochondrial signaling in adipose tissue
脂肪组织中的线粒体信号传导
  • 批准号:
    342032-2009
  • 财政年份:
    2012
  • 资助金额:
    $ 2.04万
  • 项目类别:
    Discovery Grants Program - Individual

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大麻素CB2受体:巨噬细胞efferocytosis功能调控和不稳定斑块防治的新靶点
  • 批准号:
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    2010
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    20.0 万元
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Endocannabinoid system as a therapeutic target for PVR
内源性大麻素系统作为 PVR 的治疗靶点
  • 批准号:
    10747004
  • 财政年份:
    2023
  • 资助金额:
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内源性大麻素信号传导在偏好/厌恶电路中的作用
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中央杏仁核谷氨酸回路在恐惧学习和消退中的作用
  • 批准号:
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  • 批准号:
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内源性大麻素对腹侧海马-伏隔核回路的调节及其对应激介导行为的影响
  • 批准号:
    10551206
  • 财政年份:
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Endocannabinoid regulation of ventral hippocampus-nucleus accumbens circuit and consequences for stress-mediated behaviors
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  • 批准号:
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  • 财政年份:
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Endocannabinoid-Based Treatment for the Neurologic Niemann-Pick Diseases
基于内源性大麻素的神经尼曼匹克病治疗
  • 批准号:
    10701903
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    2022
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FABP 介导的内源性大麻素信号传导食欲调节的分子驱动因素
  • 批准号:
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  • 批准号:
    10797598
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    2022
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    $ 2.04万
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