权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Functional roles of the relaxin ligand-receptor system in the thyroid

松弛素配体-受体系统在甲状腺中的功能作用

基本信息

批准号：
342187-2007
负责人：
Klonisch, Thomas
金额：
$ 2.33万
依托单位：
University of Manitoba
依托单位国家：
加拿大
项目类别：
Discovery Grants Program - Individual
财政年份：
2008
资助国家：
加拿大
起止时间：
2008-01-01 至 2009-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=399799
关键词：
Functional roles relaxin ligand receptor

项目摘要

The proposed program addresses a fundamental relationship between endocrine ligand-receptor action and structure-function cellular responses. This research program is aimed at characterizing the role of the peptide hormone relaxin (RLN) as a novel morpho-functional regulator of cytoskeletal and associated systems leading to alterations in cell movement and cell polarity in thyroid cells. We have identified the thyroid gland as a RLN target organ. In our thyroid cell models, RLN enhances cell movement, alters vesicular trafficking, and affects extracellular matrix (ECM) degradation by increasing elastinolytic cellular activity. In the present proposal we will study the molecular network which facilitates RLN-induced and LGR7 relaxin receptor-mediated changes in cell movement. Furthermore, we will study the role of relaxin on cytoskeletal filaments in polarized porcine thyroid cells and determine the effects relaxin elicits on vesicular transport in polarized porcine thyrocytes. Finally, I will create a novel transgenic mouse model with thyroglobulin-directed, thyroid-specific overexpression of LGR7 to study the effect of LGR7 stimulation on thyroid functions in-vivo. These results have significant implications for our understanding of the cellular functions of RLN and provide a unique insight into novel properties of this peptide hormone ligand-receptor system in human and animal cell biology alike.

拟议的计划解决了内分泌配体受体作用与结构功能细胞反应之间的基本关系。该研究项目旨在表征肽激素松弛素（RLN）作为细胞骨架和相关系统的新型形态功能调节剂的作用，导致甲状腺细胞中细胞运动和细胞极性的改变。我们已将甲状腺确定为 RLN 靶器官。在我们的甲状腺细胞模型中，RLN 增强细胞运动，改变囊泡运输，并通过增加弹性蛋白溶解细胞活性来影响细胞外基质 (ECM) 降解。在本提案中，我们将研究促进 RLN 诱导和 LGR7 松弛素受体介导的细胞运动变化的分子网络。此外，我们将研究松弛素对极化猪甲状腺细胞中细胞骨架丝的作用，并确定松弛素对极化猪甲状腺细胞中囊泡运输的影响。最后，我将创建一种新型转基因小鼠模型，该模型具有甲状腺球蛋白定向的、甲状腺特异性的 LGR7 过表达，以研究 LGR7 刺激对体内甲状腺功能的影响。这些结果对于我们理解 RLN 的细胞功能具有重要意义，并为这种肽激素配体-受体系统在人类和动物细胞生物学中的新特性提供了独特的见解。