TGF-BETA IN AIRWAY EPITHELIAL REPAIR

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。在对环境因素和过敏原暴露的炎症反应中，呼吸道上皮可能受到广泛的损害，部分原因是细胞凋亡。转化生长因子-β(TGF-β)可抑制上皮细胞的凋亡。鉴于转化生长因子-β在调节炎症和组织重塑中的作用，了解转化生长因子-β如何保护呼吸道上皮具有重要意义。我们将培养哮喘患者和正常人的呼吸道上皮细胞，并检测在激活Fas死亡受体后转化生长因子-b的保护作用的差异。我们将确定Smad7、细胞周期、p21和p15表达以及细胞激活的差异，这可能解释了哮喘上皮细胞对转化生长因子-β保护作用的相对抵抗。这些研究将为控制呼吸道上皮细胞动态平衡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，以保护哮喘患者的呼吸道上皮免受损害。

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.