TGF-BETA IN AIRWAY EPITHELIAL REPAIR

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在对环境因子和变应原暴露的炎症反应中，气道上皮可能广泛受损，部分原因是细胞凋亡。转化生长因子-β（TGF-β）可防止上皮细胞凋亡。鉴于TGF-β在介导炎症和组织重塑中的作用，了解TGF-β如何保护气道上皮具有重要意义。我们将培养从哮喘和正常受试者收集的气道上皮细胞，并检测Fas死亡受体激活后TGF-β保护作用的差异。我们将确定Smad 7，细胞周期，p21和p15的表达，和细胞活化的差异，可以解释哮喘上皮细胞的相对抵抗TGF-β的保护作用。这些研究将为控制气道上皮细胞稳态的基本机制提供重要的新见解。了解这一过程可能会提出新的治疗干预措施，以保护气道上皮细胞免受哮喘损伤。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The airway epithelium may be damaged extensively in inflammatory responses to environmental agents and allergen exposure, in part by apoptosis. Transforming growth factor-beta (TGF-b) may prevent epithelial cell apoptosis. Given the role of TGF-b in mediating both inflammation and tissue remodeling, Understanding how TGF-b protects airway epithelium is of importance. We will grow airway epithelium collected from asthmatic and normal subjects and examine differences in the protective effect of TGF-b after activation of the Fas death receptor. We will identify differences in Smad7, cell cycle, p21 and p15 expression, and cell activation that may explain the relative resistance of asthmatic epithelial cells to the protective effect of TGF-b. These studies should provide important new insights into a fundamental mechanism controlling airway epithelial homeostasis. Understanding the process may suggest new therapeutic interventions to protect the airway epithelium form damage in asthma.