PFKFB3-mediated glycometabolism reprogramming modulates endothelial differentiation and angiogenic capacity of placenta-derived mesenchymal stem cells

Abstract

Background Mesenchymal stem cells (MSCs) have a great potential ability for endothelial differentiation, contributing to an effective means of therapeutic angiogenesis. Placenta-derived mesenchymal stem cells (PMSCs) have gradually attracted attention, while the endothelial differentiation has not been fully evaluated in PMSCs. Metabolism homeostasis plays an important role in stem cell differentiation, but less is known about the glycometabolic reprogramming during the PMSCs endothelial differentiation. Hence, it is critical to investigate the potential role of glycometabolism reprogramming in mediating PMSCs endothelial differentiation. Methods Dil-Ac-LDL uptake assay, flow cytometry, and immunofluorescence were all to verify the endothelial differentiation in PMSCs. Seahorse XF Extracellular Flux Analyzers, Mito-tracker red staining, Mitochondrial membrane potential (MMP), lactate secretion assay, and transcriptome approach were to assess the variation of mitochondrial respiration and glycolysis during the PMSCs endothelial differentiation. Glycolysis enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) was considered a potential modulator for endothelial differentiation in PMSCs by small interfering RNA. Furthermore, transwell, in vitro Matrigel tube formation, and in vivo Matrigel plug assays were performed to evaluate the effect of PFKFB3-induced glycolysis on angiogenic capacities in this process. Results PMSCs possessed the superior potential of endothelial differentiation, in which the glycometabolic preference for glycolysis was confirmed. Moreover, PFKFB3-induced glycometabolism reprogramming could modulate the endothelial differentiation and angiogenic abilities of PMSCs. Conclusions Our results revealed that PFKFB3-mediated glycolysis is important for endothelial differentiation and angiogenesis in PMSCs. Our understanding of cellular glycometabolism and its regulatory effects on endothelial differentiation may propose and improve PMSCs as a putative strategy for clinical therapeutic angiogenesis.

Glycolysis: A fork in the path of normal and pathological pregnancy

“…166 In addition, PFKFB3 drives glycolysis, which not only regulates endothelial cell proliferation, migration, and tube formation, but also regulates endothelial differentiation and angiogenic capacity of placenta-derived mesenchymal stem cells (MSCs). 167,168 The aforementioned studies demonstrated the importance of glycolysis in preeclampsia pathogenesis and corroborated the hypothesis that the dysregulation of glycolysis leads to preeclampsia.…”

Oviduct Transcriptomic Reveals the Regulation of mRNAs and lncRNAs Related to Goat Prolificacy in the Luteal Phase

“…Moreover, some closely related reproduction pathways were annotated, such as the PI3K-Akt, MAPK, Rap1, mTOR, WNT, and calcium signaling pathways, circadian rhythm, oocyte meiosis, and fructose and mannose metabolism. Astoundingly, ALDOB [ 46 ] and PFKFB3 [ 47 , 48 ] are involved in the fructose and mannose metabolism pathways, which may provide energy for early embryonic development. This means that the prolific goats require more metabolites to maintain high fecundity.…”