摘要
      自噬参与了肺动脉高压（PAH）的调节。然而，自噬相关基因（ARGs）在PAH发病机制中的作用尚不清楚。本研究旨在通过生物信息学分析鉴定多环芳烃中的ARGs。从基因表达综合数据库下载微阵列数据集（GSE113439），以鉴定差异表达的ARGs（DEARGs）。进行了蛋白质-蛋白质相互作用网络、基因本体论和京都基因和基因组百科全书富集分析，以筛选中枢基因和PAH的潜在分子机制。最后，使用GSE53408数据集验证了枢纽基因的mRNA表达。共鉴定出26个DEARG，所有这些DEARG均上调。富集分析显示，这些DEARG主要富集于核苷酸结合寡聚化结构域（NOD）样受体信号通路、PI3K-Akt信号通路、对缺氧的反应、对营养水平的反应和自噬。在这些枢纽基因中，与健康个体相比，PAH患者的HSP90AA1、HIF1A、MET、IGF1、LRRK2、CLTC、DNM1L、MDM2、RICTOR和ROCK2的mRNA表达水平显著上调。已鉴定出10个中枢DEARG，它们可能通过自噬的调节参与PAH的发病机制。本研究可能为PAH的预防和治疗提供新的治疗靶点，并扩大我们对PAH的理解。
Abstract
Autophagy participates in the regulation of pulmonary arterial hypertension (PAH). However, the role of autophagy-related genes (ARGs) in the pathogenesis of the PAH is still unclear. This study aimed to identify the ARGs in PAH via bioinformatics analysis. A microarray dataset (GSE113439) was downloaded from the Gene Expression Omnibus database to identify differentially expressed ARGs (DEARGs). Protein–protein interactions network, gene ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to screen hub genes and the underlying molecular mechanisms of PAH. Finally, the mRNA expression of the hub genes was validated using the GSE53408 dataset. Twenty-six DEARGs were identified, all of which were upregulated. Enrichment analyses revealed that these DEARGs were mainly enriched in the nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway, PI3K-Akt signaling pathway, response to hypoxia, response to nutrient levels, and autophagy. Among these hub genes, the mRNA expression levels of HSP90AA1, HIF1A, MET, IGF1, LRRK2, CLTC, DNM1L, MDM2, RICTOR, and ROCK2 were significantly upregulated in PAH patients than in healthy individuals. Ten hub DEARGs were identified and may participate in the pathogenesis of the PAH via the regulation of autophagy. The present study may provide novel therapeutic targets for PAH prevention and treatment and expand our understanding of PAH.

https://www.degruyter.com/document/doi/10.1515/med-2022-0497/html