Shikonin reverses pyruvate kinase isoform M2‐mediated propranolol resistance in infantile hemangioma through reactive oxygen species‐induced autophagic dysfunction

Yang, Enli; Wang, Xuan; Huang, Shengyun; Li, Mingyang; Li, Yiming; Geng, Yiming; Liu, Xuejian; Chen, Zhanwei; Zhang, Dongsheng; Wu, Haiwei

doi:10.1111/cas.15649

Cited by 5 publications

(3 citation statements)

References 49 publications

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“…Furthermore, key glycolytic enzymes, including hexokinase 2,6-phosphofructo-2-kinase 3, pyruvate kinase M2 (PKM2) and lactate dehydrogenase A, are more highly expressed in HemECs than in HUVECs ( 25 ). PKM2 was demonstrated to play a critical role in regulating the progression of IH and the therapeutic resistance of propranolol treatment ( 26 ). Together, the results from these studies indicated that HemEC glucose metabolism participates in the development of IH ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated nontargeted and targeted metabolomics analyses amino acids metabolism in infantile hemangioma

et al. 2023

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Infantile hemangioma (IH) is the most common benign tumor in children. However, the exact pathogenesis of IH remains unclear. Integrated nontargeted and targeted metabolic analyses were performed to obtain insight into the possible pathogenic mechanism of IH. The results of nontargeted metabolic analysis showed that 216 and 128 differential metabolites (DMs) were identified between hemangioma-derived endothelial cells (HemECs) and HUVECs in positive-ion and negative-ion models, respectively. In both models, these DMs were predominantly enriched in pathways related to amino acid metabolism, including aminoacyl-tRNA biosynthesis and arginine and proline metabolism. Then, targeted metabolic analysis of amino acids was further performed to further clarify HemEC metabolism. A total of 22 amino acid metabolites were identified, among which only 16 metabolites, including glutamine, arginine and asparagine, were significantly differentially expressed between HemECs and HUVECs. These significant amino acids were significantly enriched in 10 metabolic pathways, including ‘alanine, aspartate and glutamate metabolism’, ‘arginine biosynthesis’, ‘arginine and proline metabolism’, and ‘glycine, serine and threonine metabolism’. The results of our study revealed that amino acid metabolism is involved in IH. Key differential amino acid metabolites, including glutamine, asparagine and arginine, may play an important role in regulating HemEC metabolism.

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Section: Discussionmentioning

confidence: 99%

Integrated nontargeted and targeted metabolomics analyses amino acids metabolism in infantile hemangioma

et al. 2023

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“…PKM2 can increase angiogenesis to support tumor growth and progression, according to a recent study [ 54 ]. Yang et al [ 55 ] mixed HemECs with overexpressed or knocked-down PKM2 with HUVECs and injected the mixture into the subcutaneous tissue of the left upper limb of 4-week-old male nude mice. Compared to the control group, knocking down PKM2 had the opposite effect on the color of the hemangioma transplants and the increase in VEGF compared to overexpression of PKM2.…”

Section: Model Of Cell Suspension Implantationmentioning

confidence: 99%

Infantile hemangioma models: is the needle in a haystack?

Kong

Wang

et al. 2023

J Transl Med

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Infantile hemangioma (IH) is the most prevalent benign vascular tumor in infants, with distinct disease stages and durations. Despite the fact that the majority of IHs can regress spontaneously, a small percentage can cause disfigurement or even be fatal. The mechanisms underlying the development of IH have not been fully elucidated. Establishing stable and reliable IH models provides a standardized experimental platform for elucidating its pathogenesis, thereby facilitating the development of new drugs and the identification of effective treatments. Common IH models include the cell suspension implantation model, the viral gene transfer model, the tissue block transplantation model, and the most recent three-dimensional (3D) microtumor model. This article summarizes the research progress and clinical utility of various IH models, as well as the benefits and drawbacks of each. Researchers should select distinct IH models based on their individual research objectives to achieve their anticipated experimental objectives, thereby increasing the clinical relevance of their findings.

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“…Recently, the metabolic activity of ECs, particularly glycolytic metabolism, has emerged as a key driver of angiogenesis (2). Yang et al discovered that PKM2, a critical glycolytic enzyme, promoted angiogenesis in HemECs, while suppression of PKM2 inhibited IH progression in a mouse model (3). Similarly, another study demonstrated that targeting FPFKB3 suppressed glycolysis and induced apoptosis in HemECs, effectively inhibiting angiogenesis (4).…”

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confidence: 99%