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The expression and role of glycolysis-associated molecules in infantile hemangioma

Aims: Infantile hemangioma (IH) is one of the most common tumors in infancy, which etiology and pathogenesis has not been fully elucidated, hypoxia and abnormal glucose metabolism is regarded as critical pathogenic factors. This study investigated the expression and function of glycolysis-associated molecules (GLUT1, HK2, PFKFB3, PKM2, and LDHA) under normoxic and hypoxic conditions to further understand the pathogenesis of IH.

Main methods: Hemangioma-derived endothelial cells (HemECs) were isolated from proliferating phase infantile hemangiomas and identified by immunofluorescence. HemECs and human umbilical vein endothelial cells (HUVECs) were cultured under normoxic and hypoxic conditions. RNA and protein expression of glycolysis-associated molecules were analyzed by quantitative real-time RT-PCR, western blotting, and immunohistochemistry. Glucose consumption, ATP production and lactate production were measured. Glycolysis-associated molecules were inhibited by WZB117, 3BP, 3PO, SKN, and GSK 2837808A and the resulting effects on HemECs proliferation, migration, and tube formation were quantified.

Key findings: Glycolysis-associated molecules were highly expressed at both mRNA and protein levels in HemECs compared with HUVECs (P < 0.05). Glucose consumption and ATP production were higher in HemECs than in HUVECs, while lactate production in HemECs was lower than in HUVECs (P < 0.05). Inhibition of some glycolysis-associated molecules reduced the proliferation, migration, and tube formation capacity of HemECs (P < 0.05).

Significance: Our study revealed that glycolysis-associated molecules were highly expressed in IH. Glucose metabolismin HemECs differed from normal endothelial cells. Altering the expression of glycolysis-associated molecules may influence the phenotype of HemECs and provide new therapeutic approaches to the successful treatment of IH.

 

Comments:

The aim of this study was to investigate the expression and function of glycolysis-associated molecules in infantile hemangioma (IH), a common tumor in infants. The researchers focused on molecules involved in glucose metabolism, as hypoxia and abnormal glucose metabolism are considered important factors in the pathogenesis of IH.

To conduct the study, the researchers isolated and identified hemangioma-derived endothelial cells (HemECs) from proliferating phase infantile hemangiomas. They also used human umbilical vein endothelial cells (HUVECs) as a comparison. HemECs and HUVECs were cultured under both normoxic (normal oxygen levels) and hypoxic (low oxygen levels) conditions.

The expression of glycolysis-associated molecules, including glucose transporter 1 (GLUT1), hexokinase 2 (HK2), 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA), was analyzed at the mRNA and protein levels using techniques such as quantitative real-time RT-PCR, western blotting, and immunohistochemistry.

The researchers also measured glucose consumption, ATP production, and lactate production in HemECs and HUVECs. They found that HemECs had higher glucose consumption and ATP production compared to HUVECs, while lactate production was lower in HemECs.

To further understand the functional implications of glycolysis-associated molecules in IH, the researchers inhibited these molecules using specific inhibitors such as WZB117, 3BP, 3PO, SKN, and GSK 2837808A. They then quantified the effects on HemECs' proliferation, migration, and tube formation capacity.

The key findings of the study were that glycolysis-associated molecules were highly expressed in HemECs compared to HUVECs. Glucose metabolism in HemECs differed from that in normal endothelial cells. Inhibiting some of the glycolysis-associated molecules reduced the proliferation, migration, and tube formation capacity of HemECs.

The significance of this study is that it sheds light on the role of glycolysis-associated molecules in IH. The altered expression of these molecules in HemECs suggests that glucose metabolism plays a crucial role in the pathogenesis of IH. Understanding these mechanisms could potentially lead to new therapeutic approaches for the treatment of IH.

Related Products

Cat.No. Product Name Information
S8590 GSK 2837808A GSK2837808A is a selective LDHA (lactate dehydrogenase A) inhibitor with IC50 of 2.6 nM and 43 nM for hLDHA and hLDHB, respectively.

Related Targets

Dehydrogenase LDH