Pathological alteration of FoxO3a in IPF pathogenesis

FoxO3a在IPF发病机制中的病理改变

基本信息

批准号：
9066198
负责人：
Richard S. Nho
金额：
$ 38万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2017-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9066198
关键词：
Accounting Adoptive Transfer Apoptosis Apoptotic Caveolae Cell Cycle Cell membrane Cells Chronic Cicatrix Collagen Collagen Type I Data Disease Feedback Fibroblasts Fibrosis Figs - dietary Funding Genetic Transcription Goals Hamman-Rich syndrome Health Immunodeficient Mouse Injury Interstitial Lung Diseases Knockout Mice Knowledge Lesion Lung Lung Transplantation Lung diseases Malignant Neoplasms Medical Modeling Molecular Myofibroblast Nature Normal tissue morphology PTEN gene Pathogenesis Pathway interactions Patients Phenotype Phosphorylation Physiological Process Proliferating Property Proteins Publishing Pulmonary Fibrosis Role Seminal Sentinel Signal Pathway Signal Transduction Signaling Molecule Smooth Muscle Actin Staining Method Specimen Staging Testing Therapeutic Transcription Coactivator Translating Work base cancer cell cell type cyclin-dependent kinase inhibitor 1B design effective therapy fibrogenesis human disease in vivo indium-bleomycin inhibitor/antagonist loss of function lung repair mouse model novel therapeutic intervention novel therapeutics prevent research study therapeutic target tissue repair upstream kinase wound

项目摘要

DESCRIPTION (provided by applicant): Idiopathic Pulmonary Fibrosis (IPF) is a deadly interstitial lung disease. Short of lung transplantation there is no proven effective treatment for the disease process. The disease is characterized by progressive scarring of the airspaces. The primary cell type responsible for the progressive scarring is the lung fibroblast. Recent work suggests that the lung fibroblast in IPF has distinct pathological properties enabling it to abnormally proliferate and survive. However, large gaps in knowledge remain regarding differences between the pathological nature of fibroblasts in IPF responsible for progressive proliferation and the limited physiological proliferation of normal fibroblasts necessary for prope lung repair. In preliminary studies, we have discovered pathological alterations in key signaling pathways that regulate IPF fibroblast proliferation and survival. This proposal seeks to further characterize key differences between normal and IPF fibroblasts that underline the aberrant ability of IPF fibroblasts to proliferate and scar airspaces. These experiments could suggest new therapeutic strategies for this lethal disease.

描述（由申请人提供）：特发性肺纤维化（IPF）是一种致命的间质性肺疾病。缺乏肺移植，没有证明有效的治疗方法疾病过程。该疾病的特征是空间的进行性疤痕。负责进行性疤痕的主要细胞类型是肺成纤维细胞。最近的工作表明，IPF中的肺成纤维细胞具有不同的病理特性，使其异常增殖和生存。然而，知识的差距仍然存在造成逐步增殖的IPF的成纤维细胞的病理性质与普通肺修复所需的正常成纤维细胞的生理增殖有限的差异。在初步研究中，我们发现了调节IPF成纤维细胞增殖和存活的关键信号通路的病理改变。该建议旨在进一步表征正常和IPF成纤维细胞之间的关键差异，这些差异强调了IPF成纤维细胞增殖和疤痕空间的异常能力。这些实验可以为这种致命疾病提出新的治疗策略。