TGF-BETA, CHLORIDE CHANNELS AND APOPTOSIS OF AIRWAY EPITHELIAL CELLS

过敏源或毒物损伤后的上皮修复包括上皮扩散和迁移到伤口的初始阶段，随后是增殖和分化以取代丢失的柱状细胞。这些过程受生长因子和细胞因子提供的局部信号在空间和时间上的调控。TGF-~在慢性哮喘亚上皮基底膜增厚、气道重塑等病理生理过程中发挥重要作用。然而，潜在的机制尚不清楚。应用中的研究将确定对TGF-诱导的凋亡敏感性的重要决定因素，这涉及气道上皮细胞中促凋亡蛋白和抗凋亡蛋白与CI通道之间的串扰。本项目的长期目标是确定TGF-~对气道上皮细胞电压门控氯离子电流的影响，并检测免疫调节剂的作用。这些研究将为慢性哮喘的病理生理过程和预防或逆转疾病的手段提供独特的见解。

Epithelial repair after an insult with allergens or toxicants consists of an initial phase of epithelial spreading and migration into the wound, followed by proliferation and differentiation to replace the columnar cells that have been lost. These processes are spatially and temporally regulated by local signals provided by growth factors and cytokines. TGF-~ plays an important role in the pathophysiology of chronic asthma including thickening of sub-epithelial basement membrane and airway remodeling. However, the underlying mechanisms are unclear. The studies in application will identify important determinants of sensitivity to TGF-~-induced apoptosis that involves cross-talk between pro- and anti-apoptotic proteins and CI- channels in airway epithelial cells. The long term goal of this project is to ascertain the effects that TGF-~ have on voltage-gated chloride currents in the airway epithelial cells and to examine the effect of immunomodulators. Such investigations would provide unique insights to the pathophysiologic process of chronic asthma and the means to prevent or reverse the disease.