Xiang Shanshan,Gong Xue,Zhou Jiangyuan,et al.Effects of glucose metabolism through a targeted inhibition of PFKFB3 on hemangioma-derived endothelial cell[J].Journal of Clinical Pediatric Surgery,2025,(10):981-987.[doi:10.3760/cma.j.cn101785-202412032-014]
靶向抑制PFKFB3对婴幼儿血管瘤内皮细胞糖代谢的影响研究
- Title:
- Effects of glucose metabolism through a targeted inhibition of PFKFB3 on hemangioma-derived endothelial cell
- Keywords:
- Hemangioma; Endothelial Cells; Glucose Metabodism; 6-Phosphofructo-2-Kinase/Fructose-2; 6-Biphosphatase 3; Infant; Young Children
- 摘要:
- 目的 探究靶向抑制6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶3(6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3,PFKFB3)对婴幼儿血管瘤内皮细胞(hemangioma-derived endothelial cell,HemEC)糖代谢的影响。方法 以未予干预的HemEC为对照组,经PFKFB3抑制剂PFK15干预的HemEC为实验组(即PFK15组)。采用高效色谱串联质谱法将对照组和实验组的HemEC进行靶向葡萄糖代谢组学检测,并对差异代谢物进行统计学分析。结果 PCA主成分分析与OPLS-DA正交偏最小二乘判别分析显示,两组代谢物差异有统计学意义(P<0.05),且OPLS-DA模型经置换检验证实稳定无过拟合[R2Y=(0, 0.27),Q2Y=(0, -1.73)]。共鉴定出45种差异代谢物,包括35种表达上调、10种表达下调代谢物。其中,三羧酸循环代谢物(苹果酸、柠檬酸、延胡索酸、α-酮戊二酸等)及糖酵解初始代谢产物(葡萄糖6磷酸、果糖6磷酸等)在PFK15组表达高于对照组,而核苷酸代谢产物(二磷酸腺苷、三磷酸腺苷等)在PFK15组表达低于对照组。45种差异代谢物中30种差异有统计学意义(P<0.05),主要富集于9条显著差异代谢通路,其中磷酸戊糖途径(P=7.53E-07,Impact=0.368)、糖酵解/糖异生(P=4.60E-05,Impact=0.278)、三羧酸循环(P=0.0003,Impact=0.126)及丙酮酸代谢(P=0.0004,Impact=0.207)为核心关联通路。结论 靶向抑制PFKFB3活性可显著影响HemEC糖代谢水平,差异代谢物主要富集在磷酸戊糖旁路途径、糖酵解/糖异生、三羧酸循环及丙酮酸代谢等与糖代谢紧密相关、差异有统计学意义的代谢通路中。
- Abstract:
- Objective To explore the effects of targeted inhibition of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) on glucose metabolism in hemangioma-derived endothelial cells (HemECs). Methods HemECs without intervention were utilized as control group while HemECs intervened by PFKFB3 inhibitor PFK15 designated as experimental group.HemECs from control and experimental groups were subjected to targeted glucose metabolomics using high-performance chromatography tandem mass spectrometry (HPLC-MS/MS).And the differential metabolites were statistically examined. Results Principal analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) revealed statistically significant differences in metabolites between the two groups (P<0.05). The OPLS-DA model was validated through permutation testing, confirming its stability and absence of overfitting (R2Y=(0, 0.27),Q2Y=(0, -1.73)). A total of 45 differentially expressed metabolites were identified, comprising 35 up-regulated and 10 down-regulated metabolites. Among these, TCA cycle metabolites (malic acid, citric acid, fumarate and α-ketoglutaric acid, etc.) and glycolytic initial metabolites (glucose-6-phosphate, fructose-6-phosphate, etc.) showed higher expression in the PFK15 group than in the control group, while nucleotide metabolites (adenosine diphosphate, adenosine triphosphate, etc.) exhibited lower expression in the PFK15 group. Among the 45 differentially expressed metabolites, 30 showed statistically significant differences (P<0.05), primarily enriched in 9 significantly altered metabolic pathways. These included the pentose phosphate pathway (P=7.53E-07, Impact=0.368), glycolysis/gluconeogenesis (P=4.60E-05, Impact=0.278), citrate cycle (P=0.0003, Impact=0.126), and pyruvate metabolism (P=0.0004, Impact=0.207) as core associated pathways. Conclusions Significant differences exist in HemEC glucose metabolism after a targeted inhibition of PFKFB3.The significantly differential metabolites are mostly enriched in metabolic pathways with statistically significant differences closely correlated with glucose metabolism,such as pentose phosphate bypass pathway,glycolysis/gluconeogenesis,tricarboxylic acid cycle and pyruvate metabolism.
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备注/Memo
收稿日期:2024-12-12。
基金项目:国家自然科学基金项目(82273556,82473553);四川省杰出青年科学基金项目(2025NFSJQ0070);四川大学从0到1创新研究项目(2022SCUH0033);四川大学医学+信息中心交叉学科建设开放项目(YGJC004);四川大学华西医院学科卓越发展1·3·5工程临床研究孵化项目(2023HXFH004);中国博士后科学基金(2023M730793);广东省基础与应用基础研究基金(2023A1515012751);广州市基础与应用基础研究基