TYPE II CELLS AND INTERSTITIAL LUNG DISEASE

II 型细胞和间质性肺疾病

• 批准号: 3844104
• 负责人: ROBERT J MASON
• 金额: --
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3844104
• 关键词: autoradiography; cell cell interaction; cell differentiation; cellular pathology; collagen; cytoskeleton; disease /disorder model; extracellular matrix; fibronectins; genetic regulation; genetic transcription; human tissue; hyperplasia; hypertrophy; immunocytochemistry; in situ hybridization; laboratory rat; laminin; pathologic process; phospholipids; posttranscriptional RNA processing; proteoglycan; pulmonary fibrosis /granuloma; pulmonary surfactants; respiratory epithelium; tissue /cell culture; tritium

Alveolar type II cells are specialized epithelial cells that line the alveolus and synthesize and secrete pulmonary surface active material. In interstitial lung disease (ILD) with extensive alveolar pathology, the composition of surface active material is abnormal which may contribute to the increased elastic recoil, alveolar collapse and fibrosis in ILD. Type II cells are also the progenitor cells for the epithelium, and proliferation of type II cells is thought to be critical for the restoration of gas exchange units after alveolar injury. This project is based on the hypotheses that type II cells are intimately involved in the pathogenesis of ILD and that the hypertrophic type II cells characteristic of ILD are functionally different from the type II cells of normal lung. The regulation of differentiated function by normal type II cells is just beginning to be understood, and we must know about normal cells before we can understand hypertrophic type II cells. We will determine the role of extracellular matrix, cytoskeletal architecture, and cell-cell interactions on the maintenance of differentiated function of normal type II cells. The importance of lung derived extracellular matrix from normal and injured lung on type II cell differentiation will be tested. Differentiated function will be assessed by transcriptional and post-transcriptional regulation of the genes for the surfactant proteins SP-A, SP-B, and SP-C and the synthesis of surfactant phospholipids. We will use immunocytochemical techniques to detect incorporated bromodeoxyuridine and proliferating cell nuclear antigen (PCNA) to demonstrate that the term "type II cell hyperplasia" describes an increase in the number of hypertrophic type II cells, only a subset of which are actually proliferating and the rest we believe are arrested in an altered state of differentiation. We will determine if the hypertrophic type II cells are synthesizing and secreting an abnormal surfactant low in phosphatidylglycerol and surfactant protein A. We will also establish if they are secreting cytokines that influence other type II cells, mesenchymal cells, or macrophages. These studies will demonstrate the importance of type II cells in the pathogenesis of ILD.

肺泡II型细胞是特化的上皮细胞， 并合成和分泌肺表面活性物质。 在 间质性肺病（ILD）伴广泛肺泡病变， 表面活性物质的组成异常，这可能有助于 ILD患者的弹性回缩增加、肺泡塌陷和纤维化。 类型 II细胞也是上皮的祖细胞，并且 II型细胞的增殖被认为是 肺泡损伤后气体交换单位的恢复。 这个项目是 基于II型细胞密切参与细胞增殖的假设， ILD的发病机制和肥大的II型细胞的特点， ILD的II型细胞在功能上不同于正常肺的II型细胞。 正常II型细胞对分化功能的调节只是 开始被理解，我们必须了解正常细胞， 能理解肥大的II型细胞 我们将决定 细胞外基质、细胞骨架结构和细胞间相互作用 维持正常II型细胞的分化功能。 的 正常和损伤肺源性细胞外基质重要性 将测试肺对II型细胞分化的影响。 差异化 将通过转录和转录后分析来评估功能。 调节表面活性蛋白SP-A、SP-B和SP-C的基因 以及表面活性剂磷脂的合成。 我们将使用 免疫细胞化学技术检测掺入的溴脱氧尿苷， 增殖细胞核抗原（PCNA），以证明该术语 “II型细胞增生”描述了细胞数量的增加， 肥大的II型细胞，其中只有一个子集实际上是 我们相信，其他的都是在一种改变了的 分化 我们将确定肥大的II型细胞是否 合成并分泌一种异常的表面活性剂， 磷脂酰甘油和表面活性剂蛋白A。 我们还将确定， 它们分泌影响其他II型细胞的细胞因子， 间充质细胞或巨噬细胞。 这些研究将证明， II型细胞在ILD发病机制中的重要性。