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The role of met receptor in morphogenesis and renewal of the intestinal epithelium

met受体在肠上皮形态发生和更新中的作用

基本信息

批准号：
342061-2008
负责人：
Saucier, Caroline
金额：
$ 2.92万
依托单位：
Université de Sherbrooke
依托单位国家：
加拿大
项目类别：
Discovery Grants Program - Individual
财政年份：
2011
资助国家：
加拿大
起止时间：
2011-01-01 至 2012-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=482420
关键词：
role met receptor morphogenesis renewal

项目摘要

The functional integrity of the intestinal epithelium in the developing and adult digestive tract relies on a tight control of proliferation, survival, migration, invasion, as well as morphogenesis of various epithelial cell populations. These events are dictated by a concerted interplay between growth factors signals produced by epithelial and surrounding mesenchymal cells. The hepatocyte growth factor (HGF) is a pleiotropic factor of mesenchymal cell origin, which is well known to promote and maintain tissue organization of various vital organs. HGF accomplishes its functions through the specific activation of the Met receptor present at the cell surface of epithelial cells. Biological processes regulated by the Met/HGF receptor axis include epithelial cells proliferation, survival, migration, invasion, as well as morphogenesis. Several lines of evidence suggest that the Met/HGF receptor axis may play key functions in the development and renewal of the intestinal epithelium. However, because of the early embryonic death of HGF or Met receptor-deficient mice, little is known about the specific role of HGF and the Met/HGF receptor in the regulation of these events The overall objective of my research program is to define the function of HGF and the Met receptor in the formation and renewal of the intestinal epithelium. For this we will exploit various cellular and molecular biological approaches applied to various epithelial models to define mechanistically the intracellular signaling pathways downstream of the Met receptor that are implicated in biological processes fundamental to the developmental morphogenesis and the renewal of the intestinal epithelium.

发育和成年消化道中肠上皮的功能完整性依赖于对各种上皮细胞群的增殖、存活、迁移、侵袭以及形态发生的严格控制。这些事件是由上皮细胞和周围间充质细胞产生的生长因子信号之间的协同相互作用决定的。肝细胞生长因子（HGF）是间充质细胞来源的多效性因子，众所周知其促进和维持各种重要器官的组织结构。 HGF通过特异性激活存在于上皮细胞的细胞表面的Met受体来实现其功能。由Met/HGF受体轴调节的生物学过程包括上皮细胞增殖、存活、迁移、侵袭以及形态发生。有证据表明，Met/HGF受体轴可能在肠上皮的发育和更新中发挥关键作用。然而，由于早期胚胎死亡的HGF或Met受体缺陷的小鼠，很少有人知道的特定作用的HGF和Met/HGF受体在这些事件的调节我的研究计划的总体目标是确定的功能的HGF和Met受体的形成和更新的肠上皮。为此，我们将利用各种细胞和分子生物学方法应用于各种上皮模型，以机械地定义Met受体下游的细胞内信号传导途径，所述细胞内信号传导途径涉及对肠上皮的发育形态发生和更新至关重要的生物过程。