Wang Min, Yan Jingjun, He Xingxing, Zhong Qiang, Zhan Chengye, Li Shusheng
Department of Emergency and Intensive Care Unit, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Biol Res. 2016 Apr 18;49:25. doi: 10.1186/s40659-016-0085-4.
Acute respiratory distress syndrome (ARDS) is a potentially devastating form of acute inflammatory lung injury as well as a major cause of acute respiratory failure. Although researchers have made significant progresses in elucidating the pathophysiology of this complex syndrome over the years, the absence of a universal detail disease mechanism up until now has led to a series of practical problems for a definitive treatment. This study aimed to predict some genes or pathways associated with sepsis-related ARDS based on a public microarray dataset and to further explore the molecular mechanism of ARDS.
A total of 122 up-regulated DEGs and 91 down-regulated differentially expressed genes (DEGs) were obtained. The up- and down-regulated DEGs were mainly involved in functions like mitotic cell cycle and pathway like cell cycle. Protein-protein interaction network of ARDS analysis revealed 20 hub genes including cyclin B1 (CCNB1), cyclin B2 (CCNB2) and topoisomerase II alpha (TOP2A). A total of seven transcription factors including forkhead box protein M1 (FOXM1) and 30 target genes were revealed in the transcription factor-target gene regulation network. Furthermore, co-cited genes including CCNB2-CCNB1 were revealed in literature mining for the relations ARDS related genes.
Pathways like mitotic cell cycle were closed related with the development of ARDS. Genes including CCNB1, CCNB2 and TOP2A, as well as transcription factors like FOXM1 might be used as the novel gene therapy targets for sepsis related ARDS.
急性呼吸窘迫综合征（ARDS）是一种潜在的毁灭性急性炎症性肺损伤形式，也是急性呼吸衰竭的主要原因。尽管多年来研究人员在阐明这种复杂综合征的病理生理学方面取得了重大进展，但迄今为止，由于缺乏通用的详细疾病机制，导致在确定治疗方法时出现了一系列实际问题。本研究旨在基于公开的微阵列数据集预测与脓毒症相关ARDS相关的一些基因或通路，并进一步探索ARDS的分子机制。
共获得122个上调的差异表达基因（DEGs）和91个下调的差异表达基因。上调和下调的DEGs主要参与有丝分裂细胞周期等功能以及细胞周期等通路。ARDS分析的蛋白质-蛋白质相互作用网络揭示了20个枢纽基因，包括细胞周期蛋白B1（CCNB1）、细胞周期蛋白B2（CCNB2）和拓扑异构酶IIα（TOP2A）。在转录因子-靶基因调控网络中揭示了包括叉头框蛋白M1（FOXM1）在内的总共7个转录因子和30个靶基因。此外，在文献挖掘中发现了包括CCNB2-CCNB1在内的与ARDS相关基因关系的共引用基因。
有丝分裂细胞周期等通路与ARDS的发展密切相关。包括CCNB1、CCNB2和TOP2A在内的基因以及FOXM1等转录因子可能用作脓毒症相关ARDS的新型基因治疗靶点。
