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丙酮酸激酶M2通过血管生成素2调节内皮细胞中的血管生成激活。

PKM2 regulates angiogenic activation via ANGPT2 in endothelial cells.

作者信息

Ge Qiangqiang, Guo Jianan, Ye Liyuan, Le Yifei, Zhu Ji

机构信息

Shangyu People's Hospital of Shaoxing, Shaoxing University, Shaoxing, 312000, China.

The Third Affiliated Hospital of Zhejiang Chinese Medical University (Zhongshan Hospital of Zhejiang Province), Hangzhou, 330061, China.

出版信息

Sci Rep. 2025 Aug 26;15(1):31448. doi: 10.1038/s41598-025-17147-2.


DOI:10.1038/s41598-025-17147-2
PMID:40858916
Abstract

Endothelial cells constitute the primary barrier within the vessel wall, exhibiting the capacity for angiogenesis, a process implicated in revascularisation.Endothelial cell-mediated angiogenesis is further recognised as a pivotal pathological factor in tumours, pulmonary hypertension, and ocular diseases. Pyruvate kinase type M2 (PKM2) represents a pivotal enzyme in glycolysis, exerting a role in the pathogenic process of diverse diseases through metabolic processes and the transcriptional regulation of key genes. This study established a correlation between PKM2 and angiogenesis in tumours, with the knockdown of PKM2 inhibiting proliferation, migration and angiogenesis in endothelial cells and the over-expression of PKM2 promoting it. Further studies identified ANGPT2 as a downstream target of PKM2, and the supplementation of endothelial cells with ANGPT2 restored proliferation, migration and angiogenesis inhibited by knockdown of PKM2. Collectively, these findings imply that ANGPT2 contributes significantly to the regulation of PKM2-mediated proliferation, migration and angiogenesis.

摘要

内皮细胞构成血管壁内的主要屏障,具有血管生成能力,这一过程与血管再生有关。内皮细胞介导的血管生成进一步被认为是肿瘤、肺动脉高压和眼部疾病中的关键病理因素。丙酮酸激酶M2型(PKM2)是糖酵解中的关键酶,通过代谢过程和关键基因的转录调控在多种疾病的致病过程中发挥作用。本研究建立了PKM2与肿瘤血管生成之间的关联,敲低PKM2可抑制内皮细胞的增殖、迁移和血管生成,而PKM2的过表达则促进这些过程。进一步研究确定血管生成素2(ANGPT2)是PKM2的下游靶点,向内皮细胞补充ANGPT2可恢复因敲低PKM2而受到抑制的增殖、迁移和血管生成。总的来说,这些发现表明ANGPT2在PKM2介导的增殖、迁移和血管生成调节中起重要作用。

相似文献

[1]
PKM2 regulates angiogenic activation via ANGPT2 in endothelial cells.

Sci Rep. 2025-8-26

[2]
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FASEB J. 2025-7-31

[3]
Inhibition of Proliferation, Migration, and Invasion by Knockdown of Pyruvate Kinase-M2 (PKM2) in Ovarian Cancer SKOV3 and OVCAR3 Cells.

Oncol Res. 2016-10-27

[4]
TYROBP overexpression alters macrophage phenotype and enhances pancreatic cancer stemness through STAT3 and PKM2 signaling.

Cell Signal. 2025-6-17

[5]
MTX2 facilitates PKM2 tetramerization to promote cardiac glucose metabolism and protects the heart against ischemia/reperfusion injury.

Theranostics. 2025-6-9

[6]
Nonalcoholic fatty liver disease and gastric bypass surgery regulate serum and hepatic levels of pyruvate kinase isoenzyme M2.

Am J Physiol Endocrinol Metab. 2018-2-20

[7]
PKM2-driven metabolic reprogramming in digestive system tumors: mechanisms, therapeutic advances, and clinical challenges.

Front Immunol. 2025-8-6

[8]
UCHL3 augments cuproptosis via PKM2 deubiquitination in hepatocellular carcinoma.

Free Radic Biol Med. 2025-9

[9]
PKM splice-switching ASOs induce upregulation of dual-specificity phosphatases and dephosphorylation of ERK1/2 in hepatocellular carcinoma.

J Biol Chem. 2025-4

[10]
PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation.

Nat Commun. 2016-10-25

本文引用的文献

[1]
Organophosphorus Flame Retardants and Metabolic Disruption: An , , and Study Focusing on Adiponectin Receptors.

Environ Health Perspect. 2024-11

[2]
Endothelial mechanobiology in atherosclerosis.

Cardiovasc Res. 2023-7-6

[3]
Angiopoietin-2-Dependent Spatial Vascular Destabilization Promotes T-cell Exclusion and Limits Immunotherapy in Melanoma.

Cancer Res. 2023-6-15

[4]
Pathological angiogenesis: mechanisms and therapeutic strategies.

Angiogenesis. 2023-8

[5]
Vascular endothelial cell development and diversity.

Nat Rev Cardiol. 2023-3

[6]
GTPBP4 promotes hepatocellular carcinoma progression and metastasis via the PKM2 dependent glucose metabolism.

Redox Biol. 2022-10

[7]
Celastrol mitigates inflammation in sepsis by inhibiting the PKM2-dependent Warburg effect.

Mil Med Res. 2022-5-20

[8]
PKM2 Is Essential for Bladder Cancer Growth and Maintenance.

Cancer Res. 2022-2-15

[9]
Angiopoietin-2: An Emerging Tie to Pathological Vessel Enlargement.

Arterioscler Thromb Vasc Biol. 2022-1

[10]
Activated mesangial cells induce glomerular endothelial cells proliferation in rat anti-Thy-1 nephritis through VEGFA/VEGFR2 and Angpt2/Tie2 pathway.

Cell Prolif. 2021-6

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