The expression and function of stress proteins in uterine smooth muscle during pregnancy
The expression and function of stress proteins in uterine smooth muscle during pregnancy
批准号:
RGPIN-2017-04951
负责人:
Macphee, Daniel
金额:
$2.04万
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
项目状态:
已结题
起止时间:
2019-01-01 至 2020-12-31
中文摘要
子宫是女性在怀孕期间容纳发育中的胎儿的器官。这个器官包含一种叫做肌层的平滑肌成分,在怀孕期间,它在分子和细胞水平上经历了一个分化和适应的过程。在肌层编程的同时,肌层和其他组织也经历了免疫系统成分的转化。这两个过程的结果是产生子宫组织,可以产生协调和强大的收缩(阵痛),以确保及时分娩足月胎儿,其器官足够成熟,可以在子宫外存活。不幸的是,我们仍然不清楚是什么控制着子宫肌瘤编程和免疫转化以及它们在怀孕期间的协调。******小应激或热休克B家族(HSPB)蛋白在细胞中具有重要的家政作用,但可以调节平滑肌的松弛和收缩。重要的是,HSPB家族成员也是免疫平衡或体内平衡的捍卫者。该程序将首次确定HSPB蛋白是否可以调节肌层内的免疫激活。此外,我们还将研究HSPA1A或HSP70 (HSPB信号的伴侣)在肌层中的表达和调控。最后,我们将首次确定这些应激蛋白是否从肌层中释放出来,用于通信目的,在称为外泌体的小包装中。本研究将利用分子和细胞生物学工具和程序,以及大鼠实验模型来实现研究目标。学员将获得独立研究、合作、项目管理、沟通和批判性思维技能等关键能力,这些能力对于在学术界、生物技术、工业或跨学科研究相关活动中取得成功的职业道路非常有价值。总的来说,这个研究项目将对怀孕期间应激蛋白如何促进子宫平滑肌功能产生更大的基础理解。
英文摘要
The uterus is a female organ that houses the developing fetus during pregnancy. This organ contains a smooth muscle component named the myometrium and during pregnancy it goes through a program of differentiation and adaptation at the molecular and cellular level. In parallel with this myometrial programming, the myometrium and other tissues also undergo transformation of immune system components. The consequence of both of these processes is the production of uterine tissue that can generate coordinated and powerful contractions (labour) to ensure the timely delivery of a term fetus whose organs are sufficiently mature for survival outside the uterus. Unfortunately, we still do not clearly understand what controls myometrial programming and immune transformation as well as their coordination during pregnancy. ******Small stress or heat shock B family (HSPB) proteins have important housekeeping roles in cells, but can regulate smooth muscle relaxation and contraction. Importantly, HSPB family members are also defenders of immunological balance or homeostasis. This program will determine for the first time whether or not HSPB proteins can modulate immunological activation within the myometrium. Furthermore, we will also investigate the expression and regulation of HSPA1A or HSP70, a partner for HSPB signaling, in the myometrium. Lastly, we will determine for the first time whether or not these stress proteins are released from myometrium, for communication purposes, within small packages called exosomes. The research will utilize molecular and cell biological tools and procedures, as well as rat experimental models to achieve the research objectives. Trainees will acquire key competencies such as independent research, collaboration, project management, communication, and critical thinking skills that are highly valuable for successful career paths in academia, biotechnology, industrial or interdisciplinary research-related activities. Overall, this research program will create a greater fundamental understanding of how stress proteins contribute to uterine smooth muscle function during pregnancy.
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