SCOR: Pathobiology of Fibrotic Lung Disease

（申请人的摘要）该SCOR提案的总体目的是 探讨肌成纤维细胞在特发性肺纤维化中的作用 （森林小组）。我们特别感兴趣的是， TGF-β的产生，特别是摄取凋亡细胞的贡献， 细胞和细胞碎片，旁分泌因子和机械 因子对肌成纤维细胞基因的调控，存活因子对 肌成纤维细胞如IGF-I和肌成纤维细胞凋亡， 肌成纤维细胞与肺泡上皮细胞，最后调节 干扰素γ（INF）。在这个SCOR建议的临床部分，博士。 施瓦茨将评价INF治疗特发性肺纤维化的效果。一 这项建议的主要方面是使用DNA微阵列来确定基因 特定细胞类型的表达以及纤维化肺中的改变， IPF和BOOP中Masson小体的显微解剖成纤维细胞灶。在 项目1，汉森博士将研究TGF-β生产的调节， 摄取凋亡细胞。这是一个新的生物过程， TGF-β的产生。在项目2中，沃森博士将研究 尤其是旁分泌与肌成纤维细胞表型之间的相互作用 例如TGF-β和机械应力。在第三个项目中，里奇斯博士将 确定IGF-1作为阻止细胞凋亡的存活因子的作用 肌成纤维细胞。在项目4中，梅森博士将研究 肌成纤维细胞和肺泡II型细胞。很大份额 该项目的目的是确定KGF，TGF-β和INF之间的相互作用， 肺泡上皮。在项目5中，施瓦茨博士将确定临床 干扰素治疗特发性肺纤维化疗效观察 IPF中的增殖和凋亡以及成纤维细胞灶中的基因表达 在BOOP的IPF和Masson体中。

(Applicant's Abstract) The overall purpose of this SCOR proposal is to investigate the role of the myofibroblast in idiopathic pulmonary fibrosis (IPF). We are particularly interested in defining the source and regulation of TGF-beta production, especially the contribution of the ingestion of apoptotic cells and cell debris, the relationship of paracrine factors and mechanical factors on myofibroblast gene regulation, the role of survival factors for myofibroblasts such as IGF- I and myofibroblast apoptosis, interactions of myofibroblasts with alveolar epithelial cells, and finally regulation by interferon gamma (INF). In the clinical portion of this SCOR proposal, Dr. Schwarz will evaluate INF in the treatment of idiopathic pulmonary fibrosis. A major aspect of this proposal will be to use DNA microarrays to define gene expression of specific cell types as well as alterations in fibrotic lung and microdissected fibroblastic foci in IPF and Masson bodies in BOOP. In project 1, Dr. Henson will study the regulation of TGF-beta production by the ingestion of apoptotic cells. This is a new biologic process for the production of TGF-beta. In project 2, Dr. Worthen will study the regulation of the myofibroblast phenotype especially the interaction between paracrine factors such as TGF-beta and mechanical stress. In project 3, Dr. Riches will determine the role of IGF-1 as a survival factor which prevents the apoptosis of myofibroblasts. In project 4, Dr. Mason will study the interactions between myofibroblasts and alveolar type II cells. A significant portion of this project is to define the interactions between KGF, TGF-beta, and INF on the alveolar epithelium. In project 5, Dr. Schwarz will determine the clinical efficacy of INF as therapy for idiopathic pulmonary fibrosis, myofibroblast proliferation and apoptosis in IPF, and gene expression in fibroblastic foci in IPF and Masson bodies of BOOP.