Ge Qiangqiang, Guo Jianan, Ye Liyuan, Le Yifei, Zhu Ji
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.
Sci Rep. 2025 Aug 26;15(1):31448. doi: 10.1038/s41598-025-17147-2.
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.
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。
