Luo Qiancheng, Ma Hanning, Guo Enwei, Yu Lin, Jia Ling, Zhang Bingyu, Feng Gang, Liu Rui
Department of Critical Care Medicine, Shanghai Pudong New Area Gongli Hospital, Shanghai, China.
Department of Emergency Medicine, General Hospital of Ningxia Medical University, Shanghai, China.
Front Neurol. 2022 Jun 9;13:909828. doi: 10.3389/fneur.2022.909828. eCollection 2022.
The objective of this study was to determine the NF-kappaB pathway, hub genes, and transcription factors (TFs) in monocytes implicated in the progression of neurovascular-related sepsis-induced cardiomyopathy (SIC) as well as potential miRNAs with regulatory functions.
: Sepsis-induced cardiomyopathy-and heart failure (HF)-related differentially expressed genes (DEGs) between SIC and HF groups were identified separately by differential analysis. In addition, DEGs and differentially expressed miRNAs (DEmiRNAs) in monocytes between sepsis and the HC group were identified. Then, common DEGs in SIC, HF, and monocyte groups were identified by intersection analysis. Based on the functional pathways enriched by these DEGs, genes related to the NF-kB-inducing kinase (NIK)/NF-kappaB signaling pathway were selected for further intersection analysis to obtain hub genes. These common DEGs, together with sepsis-related DEmiRNAs, were used to construct a molecular interplay network and to identify core TFs in the network.
: A total of 153 upregulated genes and 25 downregulated genes were obtained from SIC-, HF-, and monocyte-related DEGs. Functional pathway analysis revealed that the upregulated genes were enriched in NF-κB signaling pathway. A total of eight genes associated with NF-κB signaling pathway were then further identified from the 178 DEGs. In combination with sepsis-related DEmiRNAs, HDAC7/ACTN4 was identified as a key transcriptional regulatory pair in the progression of SIC and in monocyte regulation. hsa-miR-23a-3p, hsa-miR-3175, and hsa-miR-23b-3p can regulate the progression of SIC through the regulation of HDAC7/ACTN4. Finally, gene set enrichment analysis (GSEA) suggested that HDAC7/ACTN4 may be associated with apoptosis in addition to the inflammatory response.
: hsa-miR-23a-3p, hsa-miR-3175, and hsa-miR-23b-3p are involved in SIC progression by regulating NF-κB signaling signaling pathway-related HDAC7/ACTN4 in monocytes and cardiac tissue cells. These mechanisms may contribute to sepsis-induced neurovascular damage.
本研究的目的是确定单核细胞中与神经血管相关的脓毒症诱导的心肌病（SIC）进展相关的核因子κB（NF-κB）信号通路、枢纽基因和转录因子（TFs），以及具有调节功能的潜在微小RNA（miRNA）。
通过差异分析分别鉴定SIC组和心力衰竭（HF）组之间与脓毒症诱导的心肌病和心力衰竭相关的差异表达基因（DEGs）。此外，鉴定脓毒症组和健康对照组（HC）之间单核细胞中的DEGs和差异表达的miRNA（DEmiRNAs）。然后，通过交集分析确定SIC组、HF组和单核细胞组中的共同DEGs。基于这些DEGs富集的功能通路，选择与NF-κB诱导激酶（NIK）/NF-κB信号通路相关的基因进行进一步的交集分析以获得枢纽基因。这些共同的DEGs与脓毒症相关的DEmiRNAs一起用于构建分子相互作用网络并识别网络中的核心TFs。
从与SIC、HF和单核细胞相关的DEGs中总共获得了153个上调基因和25个下调基因。功能通路分析显示上调基因富集于NF-κB信号通路。然后从这178个DEGs中进一步鉴定出总共8个与NF-κB信号通路相关的基因。结合脓毒症相关的DEmiRNAs，HDAC7/ACTN4被确定为SIC进展和单核细胞调节中的关键转录调节对。hsa-miR-23a-3p、hsa-miR-3175和hsa-miR-23b-3p可通过调节HDAC7/ACTN4来调节SIC的进展。最后，基因集富集分析（GSEA）表明，除炎症反应外，HDAC7/ACTN4可能与细胞凋亡有关。
hsa-miR-23a-3p, hsa-miR-3175和hsa-miR-23b-3p通过调节单核细胞和心脏组织细胞中与NF-κB信号通路相关的HDAC7/ACTN4参与SIC的进展。这些机制可能导致脓毒症诱导的神经血管损伤。
