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慢性肺部疾病气道重塑的通路重建:一种系统生物学方法。

Pathway reconstruction of airway remodeling in chronic lung diseases: a systems biology approach.

作者信息

Najafi Ali, Masoudi-Nejad Ali, Ghanei Mostafa, Nourani Mohamad-Reza, Moeini Ali

机构信息

Laboratory of Systems Biology and Bioinformatics (LBB), Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.

Genomics Division, Chemical Injury Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

出版信息

PLoS One. 2014 Jun 30;9(6):e100094. doi: 10.1371/journal.pone.0100094. eCollection 2014.

DOI:10.1371/journal.pone.0100094
PMID:24978043
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4076832/
Abstract

Airway remodeling is a pathophysiologic process at the clinical, cellular, and molecular level relating to chronic obstructive airway diseases such as chronic obstructive pulmonary disease (COPD), asthma and mustard lung. These diseases are associated with the dysregulation of multiple molecular pathways in the airway cells. Little progress has so far been made in discovering the molecular causes of complex disease in a holistic systems manner. Therefore, pathway and network reconstruction is an essential part of a systems biology approach to solve this challenging problem. In this paper, multiple data sources were used to construct the molecular process of airway remodeling pathway in mustard lung as a model of airway disease. We first compiled a master list of genes that change with airway remodeling in the mustard lung disease and then reconstructed the pathway by generating and merging the protein-protein interaction and the gene regulatory networks. Experimental observations and literature mining were used to identify and validate the master list. The outcome of this paper can provide valuable information about closely related chronic obstructive airway diseases which are of great importance for biologists and their future research. Reconstructing the airway remodeling interactome provides a starting point and reference for the future experimental study of mustard lung, and further analysis and development of these maps will be critical to understanding airway diseases in patients.

摘要

气道重塑是一种在临床、细胞和分子水平上与慢性阻塞性气道疾病相关的病理生理过程,这些疾病包括慢性阻塞性肺疾病(COPD)、哮喘和芥子气肺。这些疾病与气道细胞中多种分子途径的失调有关。迄今为止,以整体系统的方式发现复杂疾病的分子病因方面进展甚微。因此,途径和网络重建是解决这一具有挑战性问题的系统生物学方法的重要组成部分。在本文中,我们使用多个数据源构建了以芥子气肺作为气道疾病模型的气道重塑途径的分子过程。我们首先编制了一份在芥子气肺疾病中随气道重塑而变化的基因主列表,然后通过生成和合并蛋白质 - 蛋白质相互作用和基因调控网络来重建途径。实验观察和文献挖掘被用于识别和验证该主列表。本文的结果可为密切相关的慢性阻塞性气道疾病提供有价值的信息,这对生物学家及其未来的研究非常重要。重建气道重塑相互作用组为芥子气肺的未来实验研究提供了一个起点和参考,对这些图谱的进一步分析和拓展对于理解患者的气道疾病至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba83/4076832/11c1438a780a/pone.0100094.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba83/4076832/24272b3c9d56/pone.0100094.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba83/4076832/69bc9610c2d0/pone.0100094.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba83/4076832/b4c2ecb9c8e6/pone.0100094.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba83/4076832/11c1438a780a/pone.0100094.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba83/4076832/24272b3c9d56/pone.0100094.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba83/4076832/69bc9610c2d0/pone.0100094.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba83/4076832/b4c2ecb9c8e6/pone.0100094.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba83/4076832/11c1438a780a/pone.0100094.g004.jpg

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本文引用的文献

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Microarray gene expression analysis of the human airway in patients exposed to sulfur mustard.暴露于硫芥的患者气道的基因芯片基因表达分析。
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The BioGRID interaction database: 2013 update.生物信息学研究协作资源(BioGRID)交互数据库:2013 年更新
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单克隆抗体对丝氨酸蛋白酶抑制剂E2/蛋白酶连接蛋白-1的抑制作用可减轻哮喘小鼠模型中的气道重塑。
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