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,,():981-987.[doi:10.3760/cma.j.cn101785-202412032-014]
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
- 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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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