SCOR: Pathobiology of Fibrotic Lung Disease

(申请人摘要)这项SCOR建议的总体目的是 肌成纤维细胞在特发性肺纤维化中的作用 (IPF)。我们特别感兴趣的是确定 转化生长因子β的产生，特别是对细胞凋亡的摄取的贡献 细胞和细胞碎片、旁分泌因子与机械的关系 影响肌成纤维细胞基因调控的因素中，存活因子对 IGF-I等肌成纤维细胞与肌成纤维细胞凋亡的相互作用 肌成纤维细胞与肺泡上皮细胞，最后通过调节 干扰素γ(INF)。在这项SCOR提案的临床部分，Dr。 施瓦茨将评估INF在特发性肺纤维化治疗中的作用。一个 这项提议的主要方面将是使用DNA微阵列来定义基因 肝纤维化肺组织中特定细胞类型的表达及变化 显微解剖IPF和BOOP的Masson小体的成纤维细胞灶。在……里面 项目1，汉森博士将研究转化生长因子-β产生的调节。 吞噬凋亡细胞。这是一种新的生物过程 转化生长因子-β的产生。在项目2中，沃森博士将研究这一规定 肌成纤维细胞的表型，尤其是旁分泌之间的相互作用 转化生长因子-β和机械应力等因素。在项目3中，理查斯博士将 确定IGF-1作为一种阻止细胞凋亡的生存因子的作用 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。其中很大一部分 该项目旨在定义KGF、转化生长因子-β和干扰素之间的相互作用 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的疗效观察 肺间质纤维化的增殖、凋亡及成纤维细胞灶中基因的表达 在Boop的IPF和Masson小体中。

(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.