Role of fibrin-integrin interactions in supporting 2D and 3D pancreatic islet growth and function

纤维蛋白-整合素相互作用在支持 2D 和 3D 胰岛生长和功能中的作用

基本信息

批准号：
239981-2011
负责人：
Wang, Rennian
金额：
$ 3.5万
依托单位：
University of Western Ontario
依托单位国家：
加拿大
项目类别：
Discovery Grants Program - Individual
财政年份：
2013
资助国家：
加拿大
起止时间：
2013-01-01 至 2014-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=524646
关键词：
Role fibrin integrin interactions supporting

项目摘要

The discovery of insulin in 1921 by Banting and Best laid the foundation for the modern management of diabetes mellitus. However, insulin treatment cannot cure diabetes and will not prevent the secondary complications that are responsible for the devastating morbidity and mortality of this disease. Replacement of insulin-producing cells through islet transplantation has the best chance to prevent, reverse or stabilize these complications. However, the scarcity of islets and limitations in our knowledge of the factors influencing islet biology present a major obstacle precluding islet transplantation from being adopted as a routine treatment. Advancement in this field requires a thorough understanding of the developmental biology of the pancreas. In the present application we propose to identify specific factors that are responsible for the maintenance of insulin-producing cells. Our focus is on the role of integrins, membrane receptors that are known to interact with extracellular matrix proteins to control several aspects of pancreatic organogenesis and tissue maintenance. We will characterize these receptors on insulin-producing cells, examine their interactions with one specific matrix protein, fibrin, and study the mechanisms by which these interactions regulate survival of insulin-producing cells. It is our hope that these studies will facilitate the development of appropriate tissue engineering strategies for a bioartificial endocrine pancreas. This treatment will have far-reaching economic and social benefits.

1921年通过Banting和最佳糖尿病管理基础发现胰岛素的发现。但是，胰岛素治疗无法治愈糖尿病，并且不会阻止导致该疾病毁灭性发病率和死亡率的次要并发症。通过胰岛移植替换产生胰岛素的细胞是预防，逆转或稳定这些并发症的最佳机会。但是，在我们对影响胰岛生物学因素的知识中，胰岛缺乏和局限性提出了一种主要的障碍，排除了从被采用作为常规治疗的胰岛移植。该领域的进步需要对胰腺的发育生物学有深入的了解。在本应用中，我们建议确定负责维持胰岛素产生细胞的特定因素。我们的重点是已知与细胞外基质蛋白相互作用的整合素，膜受体的作用，以控制胰腺器官发生和组织维持的几个方面。我们将在产生胰岛素的细胞上表征这些受体，检查它们与一种特定基质蛋白，纤维蛋白的相互作用，并研究这些相互作用调节产生胰岛素生成细胞存活的机制。我们希望这些研究将促进生物人工内分泌胰腺的适当组织工程策略的发展。这种治疗将具有深远的经济和社会利益。