Placenta · 2026
Piezo1 modulates PFKFB3 during placental neovascularization in preeclampsia via YAP to regulate glycolysis in endothelial progenitor cells.
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Chen Yangyang, Wan Gui, Liu Xiaoxia, Li Lun, Zhang Yang, Gao Hui, Wang Qianhua, Jin Zhishan, Tao Hui, Wu Di, Zhao Yin, Zou Li, Liu Weifang
Аннотация
INTRODUCTION: Preeclampsia (PE) is a pregnancy-related disorder that contributes to substantial maternal and fetal mortality when accompanied by severe clinical manifestations. Previous studies have reported that endothelial progenitor cells (EPCs) play an important role in regulating vascular homeostasis in PE. However, the relationship between Piezo1 and glycolysis in EPCs during vascular repair in PE remains poorly understood.
METHODS: EPCs were isolated from human umbilical cord blood using density gradient centrifugation. Quantitative real-time PCR, Western blot, and immunocytochemistry were performed to detect gene expression levels. RNA-seq was performed to identify differentially expressed genes after Piezo1 activation. EdU, tube formation, and transwell assays were conducted to evaluate the functional capacities of EPCs. A preeclamptic mouse model was used to investigate the effects of EPC transplantation.
RESULTS: Downregulated levels of Piezo1 and PFKFB3 were observed in EPCs from patients with PE. Activation of Piezo1 increased intracellular Ca2+ concentration and YAP dephosphorylation in EPCs. Furthermore, nuclear translocation of YAP promoted the expression of PFKFB3, which enhanced glycolysis in EPCs. Meanwhile, transplantation of Yoda1-treated EPCs improved placental vascularization, alleviated PE-like manifestations, and enhanced pregnancy outcomes in a PE-like mouse model. Our study demonstrated that activation of Piezo1 promotes EPC-mediated neovascularization through increased glycolysis via the YAP/PFKFB3 pathway both in vitro and in vivo.
DISCUSSION: The Piezo1/YAP/PFKFB3 axis plays a significant role in EPC function. The present findings reveal a novel regulatory mechanism in EPCs relevant to PE and suggest that EPC transplantation may represent a promising potential therapeutic approach for PE.
METHODS: EPCs were isolated from human umbilical cord blood using density gradient centrifugation. Quantitative real-time PCR, Western blot, and immunocytochemistry were performed to detect gene expression levels. RNA-seq was performed to identify differentially expressed genes after Piezo1 activation. EdU, tube formation, and transwell assays were conducted to evaluate the functional capacities of EPCs. A preeclamptic mouse model was used to investigate the effects of EPC transplantation.
RESULTS: Downregulated levels of Piezo1 and PFKFB3 were observed in EPCs from patients with PE. Activation of Piezo1 increased intracellular Ca2+ concentration and YAP dephosphorylation in EPCs. Furthermore, nuclear translocation of YAP promoted the expression of PFKFB3, which enhanced glycolysis in EPCs. Meanwhile, transplantation of Yoda1-treated EPCs improved placental vascularization, alleviated PE-like manifestations, and enhanced pregnancy outcomes in a PE-like mouse model. Our study demonstrated that activation of Piezo1 promotes EPC-mediated neovascularization through increased glycolysis via the YAP/PFKFB3 pathway both in vitro and in vivo.
DISCUSSION: The Piezo1/YAP/PFKFB3 axis plays a significant role in EPC function. The present findings reveal a novel regulatory mechanism in EPCs relevant to PE and suggest that EPC transplantation may represent a promising potential therapeutic approach for PE.