The expression and function of stress proteins in uterine smooth muscle during pregnancy

妊娠期子宫平滑肌应激蛋白的表达及功能

• 批准号: RGPIN-2017-04951
• 负责人: MacPhee, Daniel
• 金额: $ 2.04万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=658364
• 关键词: expression; function; stress; proteins; uterine

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.

子宫是女性器官，在怀孕期间容纳发育中的胎儿。这个器官包含一个名为子宫肌层的平滑肌成分，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程序。与这种子宫肌层编程并行，子宫肌层和其他组织也经历免疫系统组分的转化。这两个过程的结果是子宫组织的产生，可以产生协调和强大的收缩（分娩），以确保足月胎儿的及时分娩，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层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（HSP B）蛋白在细胞中具有重要的管家作用，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稳态的捍卫者。该计划将首次确定HSPB蛋白是否可以调节子宫肌层内的免疫激活。此外，我们还将研究子宫肌层中HSPA1A或HSP70（HSPB信号的伴侣）的表达和调控。最后，我们将首次确定这些应激蛋白是否从子宫肌层中释放出来，用于通信目的，在称为外泌体的小包装中。该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。学员将获得关键能力，如独立研究，协作，项目管理，沟通和批判性思维技能，这些技能对于学术界，生物技术，工业或跨学科研究相关活动的成功职业道路非常有价值。总的来说，这项研究计划将创造一个更大的基本了解如何应激蛋白有助于子宫平滑肌功能在怀孕期间。