Neonatal Intensive Care Unit, Liaocheng Dongchangfu People's Hospital, Liaocheng 252000, China.
Neonatal Intensive Care Unit, Liaocheng Dongchangfu Maternal and Child Health Care Hospital, Liaocheng 252000, China.
Biomed Res Int. 2021 Apr 6;2021:5568724. doi: 10.1155/2021/5568724. eCollection 2021.
Necrotizing enterocolitis (NEC) is one of the most serious gastrointestinal disease-causing high morbidity and mortality in premature infants. However, the underlying mechanism of the pathogenesis of NEC is still not fully understood.
RNA sequencing of intestinal specimens from 9 NEC and 5 controls was employed to quantify the gene expression levels. RNA sequencing was employed to quantify the gene expression levels. DESeq2 tool was used to identify the differentially expressed genes. The biological function, pathways, transcription factors, and immune cells dysregulated in NEC were characterized by gene set enrichment analysis.
In the present study, we analyzed RNA sequencing data of NECs and controls and revealed that immune-related pathways were highly activated, while some cellular responses to external stimuli-related pathways were inactivated in NEC. Moreover, B cells, macrophages M1, and plasma cells were identified as the major cell types involved in NEC. Furthermore, we also found that inflammation-related transcription factor genes, such as STAT1, STAT2, and IRF2, were significantly activated in NEC, further suggesting that these TFs might play critical roles in NEC pathogenesis. In addition, NEC samples exhibited heterogeneity to some extent. Interestingly, two subgroups in the NEC samples were identified by hierarchical clustering analysis. Notably, B cells, T cells, Th1, and Tregs involved in adaptive immune were predicted to highly infiltrate into subgroup I, while subgroup II was significantly infiltrated by neutrophils. The heterogeneity of immune cells in NEC indicated that both innate and adaptive immunes might induce NEC-related inflammatory response.
In summary, we systematically analyzed inflammation-related genes, signaling pathways, and immune cells to characterize the NEC pathogenesis and samples, which greatly improved our understanding of the roles of inflammatory responses in NEC.
坏死性小肠结肠炎（NEC）是导致早产儿高发病率和死亡率的最严重胃肠道疾病之一。然而，NEC 的发病机制的潜在机制仍未完全了解。
采用 RNA 测序技术对 9 例 NEC 患儿和 5 例对照患儿的肠道标本进行基因表达水平定量分析。采用 DESeq2 工具鉴定差异表达基因。通过基因集富集分析，对 NEC 中失调的生物学功能、途径、转录因子和免疫细胞进行特征分析。
本研究分析了 NEC 和对照的 RNA 测序数据，结果表明免疫相关途径高度激活，而 NEC 中某些细胞对外界刺激的反应途径失活。此外，B 细胞、巨噬细胞 M1 和浆细胞被鉴定为参与 NEC 的主要细胞类型。此外，我们还发现，炎症相关转录因子基因如 STAT1、STAT2 和 IRF2 在 NEC 中显著激活，进一步表明这些 TF 在 NEC 发病机制中可能发挥关键作用。此外，NEC 样本在某种程度上表现出异质性。有趣的是，通过层次聚类分析，在 NEC 样本中鉴定出两个亚组。值得注意的是，参与适应性免疫的 B 细胞、T 细胞、Th1 和 Treg 被预测高度浸润到亚组 I 中，而亚组 II 则被中性粒细胞显著浸润。NEC 中免疫细胞的异质性表明固有免疫和适应性免疫均可能引发与 NEC 相关的炎症反应。
总之，我们系统地分析了炎症相关基因、信号通路和免疫细胞，以表征 NEC 的发病机制和样本，这极大地提高了我们对炎症反应在 NEC 中的作用的理解。
