Characterization of miRNA Expression in Idiopathic Pulmonary Fibrosis (IPF)

描述(由申请人提供)： 摘要：特发性肺纤维化(IPF)是一种破坏性的肺部疾病，可导致肺组织的正常结构/功能丧失和永久性瘢痕形成。导致这种情况发展的细胞和分子变化在很大程度上仍然未知。新出现的文献表明，miRNAs在正常发育和疾病中发挥重要作用，如肺发育和肺癌、糖尿病和心力衰竭。然而，对IPF中的miRNAs知之甚少。我们之前已经报道了发育中的肺中microRNA机制的关键组件。我们的初步研究已经确定了几个选择性地富含在胚胎和成人肺中的microRNAs。在这里，我们假设IPF可能具有细胞类型特异性的miRNA表达特征，并且这些特征的特征可能为识别疾病生物标志物和治疗靶点提供基础。我们建议可以利用肺组织研究联盟(LTRC)的组织和我们小组已经建立的方法来识别和进一步表征miRNA签名。本研究提出了两个特定的目标：目的1：利用miRNA微阵列技术检测IPF患者肺组织中miRNAs的表达水平与正常对照肺组织相比显著下调或上调。目的：应用原位杂交技术研究这些miRNAs在特发性肺纤维化患者肺组织切片中的表达模式，并与正常肺组织进行比较。这些研究的结果可能为了解miRNAs在IPF发病机制中的作用提供新的见解，并有助于设计其诊断和治疗策略。(摘要结束) 公共卫生相关性： 项目简介特发性肺纤维化(IPF)是一种破坏性的肺部疾病，会导致正常结构/功能的丧失和肺组织的永久性疤痕。IPF在美国人口中的发病率为30/10万。目前，IPF的自然原因尚不清楚，也没有有效的治疗方法，中位生存期为2.8-4.2年。对miRNAs功能的研究已经对肺癌、糖尿病和心力衰竭等几种危重疾病产生了巨大的影响。然而，对IPF中的miRNAs知之甚少。我们之前已经报道了发育中的肺中microRNA机制的关键组件。我们的初步研究已经确定了几个选择性地富含在胚胎和成人肺中的microRNAs。在这里，我们假设IPF可能具有细胞类型特异性的miRNA表达特征，并且这些特征的特征可能为识别疾病生物标志物和治疗靶点提供基础。我们认为，通过使用microRNA阵列和原位杂交方法以及利用肺组织研究联盟(LTRC)的组织，可以识别和进一步表征miRNA特征。

DESCRIPTION (provided by applicant): Abstract: Idiopathic Pulmonary Fibrosis (IPF) is a devastating disease of the lung that may lead to loss of normal structure/function and permanent scarring of the lung tissue. The cellular and molecular changes that lead to the development of this condition are still largely unknown. There is emerging literature showing that miRNAs play essential roles in normal development and in diseases, such as lung development and lung cancer, diabetes and heart failure. Nothing, however, is known about miRNAs in IPF. We have previously reported critical components of the microRNA machinery in the developing lungs. Our preliminary studies have identified several microRNAs selectively enriched in the embryonic and adult lung. Here we hypothesize that IPF may have cell type specific miRNA expression signatures, and that characterizing these signatures may provide the basis for the identification of disease biomarkers and therapeutic targets. We propose that miRNA signatures can be identified and further characterized by utilizing the tissues from Lung Tissue Research Consortium (LTRC) and methodologies already established in our group. Two specific Aims are proposed for this study: Aim 1: to identify miRNAs significantly down- or up-regulated in lung tissue from IPF patients compared to control non-affected lungs by using miRNA microarray. Aim 2: to characterize the expression pattern of these miRNAs in histological sections from IPF patients and compare with control morphologically normal lungs by using in situ hybridization. Results from these studies may provide novel insights into the role of miRNAs in the pathogenesis of IPF, and help to design strategies for its diagnosis and management. (End of Abstract) PUBLIC HEALTH RELEVANCE: Project Narrative Idiopathic Pulmonary Fibrosis (IPF) is a devastating disease of the lung that leads to loss of normal structure/function and permanent scarring of the lung tissue. The incidence of IPF in the U.S. population is 30/100,000. Currently, the natural cause of IPF is unknown, and there are no effective treatments with a median survival of 2.8-4.2 yrs. The studying the function of miRNAs has made huge impact on several critical disease, such as lung cancer, diabetes and heart failure. Nothing, however, is known about miRNAs in IPF. We have previously reported critical components of the microRNA machinery in the developing lungs. Our preliminary studies have identified several microRNAs selectively enriched in the embryonic and adult lung. Here we hypothesize that IPF may have cell type specific miRNA expression signatures, and that characterizing these signatures may provide the basis for the identification of disease biomarkers and therapeutic targets. We propose that miRNA signatures can be identified and further characterized by using microRNA array and in situ hybridization approaches and utilizing the tissues from Lung Tissue Research Consortium (LTRC).