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

doi:10.3969/j.issn.1006-5725.2026.07.013

Abstract

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.

Key words: proliferation, Yes-associated protein, AMP-activated protein kinase, glycolysis

CLC Number:

R543.2

Rui KE,Wei ZHANG,Ping HE,Wenhua SHI,Yonghong ZHANG. AMPK activation inhibits pulmonary arterial smooth muscle cells proliferation via YAP/PKM2/glycolysis signaling pathway[J]. The Journal of Practical Medicine, 2026, 42(7): 1208-1214.

Figures/Tables 7

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References 25

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组别	糖酵解能力	糖酵解容量	乳酸产生量
对照组	17.86 ± 0.68	37.68 ± 3.18	1.00 ± 0.16
S1P组	32.06 ± 1.79^*	73.80 ± 4.45^*	1.89 ± 0.25^*
t值	-12.84	-11.446	-7.324
P值	0.00	0.00	0.00

组别	糖酵解能力	糖酵解容量	乳酸产生量
对照组	15.32 ±2.71	41.21 ± 0.91	1.00 ± 0.15
S1P组	35.20 ± 3.56^*	77.11 ± 2.70^*	1.80 ± 0.23^*
con siRNA + S1P组	33.12 ± 5.32^*	74.09 ± 2.51^*	1.76 ± 0.19^*
YAP siRNA + S1P组	20.99 ± 2.49^#	48.37 ± 2.38^#	1.17 ± 0.17^#
F值	20.12	194.58	27.29
P值	0.00	0.00	0.00

组别	糖酵解能力	糖酵解容量	乳酸产生量
对照组	15.68 ±0.08	40.60 ± 2.51	1.00 ± 0.05
S1P组	31.41 ± 5.89^*	81.46 ± 2.72^*	1.81 ± 0.18^*
MET组	14.70 ± 0.97	39.75 ± 1.76	0.94 ± 0.04
S1P + MET组	20.25 ±1.54^#	45.00 ± 0.90^#	1.14 ± 0.22^#
F值	81.99	271.84	45.45
P值	0.00	0.00	0.00

AMPK activation inhibits pulmonary arterial smooth muscle cells proliferation via YAP/PKM2/glycolysis signaling pathway

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