The role of met receptor in morphogenesis and reewal 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。 肝细胞生长因子（hepatocyte growth factor，HGF）是一种来源于间充质细胞的多效性因子，它能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，在体外和体内，以定义机械细胞内信号转导通路下游的Met受体，涉及的生物过程的发展和更新的肠上皮细胞的基础。

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 presents 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 know 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, both in vitro and in vivo, to define mechanistically intracellular signaling pathways downstream of the Met receptor that are implicated in biological processes fundamental to the development and the renewal of the intestinal epithelium.