Ran Min, Yin Li, Guo Yatu, Zhang Wei
Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, 300070, China.
Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital, Tianjin, 300020, China.
Curr Med Chem. 2025;32(23):4805-4815. doi: 10.2174/0109298673293975240214091034.
The aims of this study are to discover dysregulated adipocytokine signaling pathway and pyroptosis-related genes to predict neonatal hypoxic-ischemic encephalopathy (HIE) occurrence.
HIE is an important cause of infant death and long-term neurological sequelae. Current treatment options for HIE are relatively limited and the pathogenesis of HIE remains to be fully explored. This study investigated the alterations of adipocytokine signaling pathway and pyroptosis in neonatal HIE.
To reveal the alterations of adipocytokine signaling pathway and pyroptosis relevant to HIE occurrence.
Data on neonatal HIE were downloaded from the Gene Expression Omnibus (GEO) database. Pathway analyses of single-sample gene set enrichment analysis (ss- GSEA) and GSEA were performed on the adipocytokine signaling pathway and pyroptosis. Proportions of immune cells in a single sample were also calculated by ssGSEA and CIBERSORT algorithm. The relationship between the adipocytokine signaling pathway and pyroptosis was analyzed according to Pearson correlation analysis.
The activities of KEGG pathways changed after the occurrence of HIE, and adipocytokine signaling pathway was activated with related overexpressed genes. For the three energy metabolisms, carbohydrate metabolism was enhanced; lipid metabolism showed increased fatty acids metabolism and decreased ability of fatty acids synthesis; metabolic levels of phosphate and phenylalanine in amino acid metabolism were elevated. Enhanced pyroptosis and relevant overexpressed genes were accompanied by increased immune cells. A positive connection between adipocytokine signaling pathway and pyroptosis was observed.
These results indicated that the adipocytokine signaling pathway may promote HIE occurrence by upregulating the expression of pyroptosis-related genes, providing a novel mechanism for HIE.
本研究旨在发现失调的脂肪细胞因子信号通路和与细胞焦亡相关的基因，以预测新生儿缺氧缺血性脑病（HIE）的发生。
HIE是婴儿死亡和长期神经后遗症的重要原因。目前HIE的治疗选择相对有限，其发病机制仍有待充分探索。本研究调查了新生儿HIE中脂肪细胞因子信号通路和细胞焦亡的变化。
揭示与HIE发生相关的脂肪细胞因子信号通路和细胞焦亡的变化。
从基因表达综合数据库（GEO）下载新生儿HIE的数据。对脂肪细胞因子信号通路和细胞焦亡进行单样本基因集富集分析（ss-GSEA）和基因集富集分析（GSEA）的通路分析。还通过ssGSEA和CIBERSORT算法计算单个样本中免疫细胞的比例。根据Pearson相关性分析脂肪细胞因子信号通路与细胞焦亡之间的关系。
HIE发生后KEGG通路的活性发生变化，脂肪细胞因子信号通路被激活，相关基因过表达。对于三种能量代谢，碳水化合物代谢增强；脂质代谢显示脂肪酸代谢增加，脂肪酸合成能力下降；氨基酸代谢中磷酸盐和苯丙氨酸的代谢水平升高。细胞焦亡增强和相关基因过表达伴随着免疫细胞增加。观察到脂肪细胞因子信号通路与细胞焦亡之间存在正相关。
这些结果表明，脂肪细胞因子信号通路可能通过上调细胞焦亡相关基因的表达促进HIE的发生，为HIE提供了一种新机制。
