实用医学杂志2026，Vol.42Issue(7)：1208-1214,7.DOI:10.3969/j.issn.1006-5725.2026.07.013
AMPK调控YAP/PKM2/糖酵解信号通路抑制肺动脉平滑肌细胞增殖的机制
AMPK activation inhibits pulmonary arterial smooth muscle cells proliferation via YAP/PKM2/glycolysis signaling pathway
摘要
Abstract
Objective To investigate the molecular mechanism by which Yes-associated protein(YAP)regulates glycolysis during pulmonary arterial smooth muscle cell(PASMC)proliferation,and to identify potential therapeutic targets.Methods Primary cultured PASMC were stimulated with sphingosine-1-phosphate(S1P).YAP phosphorylation and pyruvate kinase(PKM2)protein expression were determined by Western blot.Cellular glycolytic function was assessed by measuring the glycolysis rate with a seahorse metabolic analyzer and quantifying lactate production using a lactate assay kit.Cell proliferation was analyzed by a BrdU incorporation assay.Results Compared with the control group,the S1P group showed significantly reduced p-YAP level,increased PKM2 protein expression,enhanced glycolytic capacity,and elevated lactate production in the culture medium(P＜0.05).Knockdown of YAP with specific siRNA attenuated S1P-induced PKM2 upregulation,as well as the enhancement of glycolytic capacity and lactate production(P＜0.05).Furthermore,activation of AMPK by metformin inhibited YAP activity,thereby reversing S1P-induced upregulation of PKM2,enhanced glycolysis,and lactate production(P＜0.05).Finally,interventions with YAP siRNA transfection,the glycolysis inhibitor 2-DG,and the AMPK activator metformin mitigated S1P-induced PASMC proliferation(P＜0.05).Conclusion S1P promotes PASMC proliferation through the YAP/PKM2/glycolysis signaling pathway,while metformin activates AMPK to inhibit this pathway,thereby suppressing PASMC proliferation.关键词
细胞增殖/Yes相关蛋白/AMPK/糖酵解Key words
proliferation/Yes-associated protein/AMP-activated protein kinase/glycolysis分类
医药卫生引用本文复制引用
柯蕊,张伟,和平,史文花,张永红..AMPK调控YAP/PKM2/糖酵解信号通路抑制肺动脉平滑肌细胞增殖的机制[J].实用医学杂志,2026,42(7):1208-1214,7.基金项目
国家自然科学基金项目(编号:82100067) （编号:82100067）
陕西省自然科学基金项目(编号:2024JC-YBQN-0833) （编号:2024JC-YBQN-0833）
