基因
肺动脉高压
免疫系统
病理生理学
基因表达
纤维化
肺纤维化
基因表达谱
淋巴细胞
医学
生物信息学
癌症研究
生物
免疫学
病理
遗传学
内科学
作者
Hui Zhao,Lan Wang,Yan Yi,Zhao Qinhua,Jing He,Rong Jiang,Ci‐Jun Luo,Hong‐Ling Qiu,Yuqing Miao,Shan Shan Gong,Ping Yuan,Wen-Hui Wu
标识
DOI:10.3389/fimmu.2023.1197752
摘要
Pulmonary fibrosis (PF) and pulmonary hypertension (PH) have common pathophysiological features, such as the significant remodeling of pulmonary parenchyma and vascular wall. There is no effective specific drug in clinical treatment for these two diseases, resulting in a worse prognosis and higher mortality. This study aimed to screen the common key genes and immune characteristics of PF and PH by means of bioinformatics to find new common therapeutic targets. Expression profiles are downloaded from the Gene Expression Database. Weighted gene co-expression network analysis is used to identify the co-expression modules related to PF and PH. We used the ClueGO software to enrich and analyze the common genes in PF and PH and obtained the protein–protein interaction (PPI) network. Then, the differential genes were screened out in another cohort of PF and PH, and the shared genes were crossed. Finally, RT-PCR verification and immune infiltration analysis were performed on the intersection genes. In the result, the positive correlation module with the highest correlation between PF and PH was determined, and it was found that lymphocyte activation is a common feature of the pathophysiology of PF and PH. Eight common characteristic genes ( ACTR2, COL5A2, COL6A3, CYSLTR1, IGF1, RSPO3, SCARNA17 and SEL1L ) were gained. Immune infiltration showed that compared with the control group, resting CD4 memory T cells were upregulated in PF and PH. Combining the results of crossing characteristic genes in ImmPort database and RT-PCR, the important gene IGF1 was obtained. Knocking down IGF1 could significantly reduce the proliferation and apoptosis resistance in pulmonary microvascular endothelial cells, pulmonary smooth muscle cells, and fibroblasts induced by hypoxia, platelet-derived growth factor-BB (PDGF-BB), and transforming growth factor-β1 (TGF-β1), respectively. Our work identified the common biomarkers of PF and PH and provided a new candidate gene for the potential therapeutic targets of PF and PH in the future.
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