Effect of MSC-derived EVs induced by AGEs on energy metabolism in vascular endothelial cells DOI Creative Commons
Jiabin Liang,

Sihang Cheng,

Qi-De Song

et al.

Kidney International Reports, Journal Year: 2024, Volume and Issue: 10(1), P. 227 - 246

Published: Oct. 22, 2024

Advanced glycation end products (AGEs) play a critical role in the development of vascular diseases diabetes. Although stem cell therapies often involve exposure to AGEs, impact this environment on extracellular vesicles (EVs) and endothelial metabolism remains unclear. Human umbilical cord mesenchymal cells (MSCs) were treated with either 0 ng/ml or 100 AGEs serum-free medium for 48 hours, after which MSC-EVs isolated. The EVs characterized by morphology, particle size, protein markers MSC-EVs, microRNA (miRNA) sequencing was performed identify differentially expressed miRNAs. cocultured human vein (HUVECs) assess effects viability, metabolic activity, oxidative stress, antioxidant capacity. Tube formation glucose transporter analyses conducted evaluate angiogenic ability ranged from 30 150 nm, is consistent exosomal properties. treatment reduced MSC viability but had minimal effect EV morphology markers. miRNA showed downregulation hsa-miR-223-3p hsa-miR-126-3p_R-1, upregulation hsa-miR-574-5p, implicating changes glycolytic phosphorylation pathways. decreased HUVEC (P < 0.05), pH adenosine triphosphate (ATP) while enhancing glycolysis processes, including capacity, reserve 0.05). This likely resulted impaired mitochondrial function, ATP production, maximal respiration, basal spare respiratory capacity increased reactive oxygen species (ROS) 0.05) glucose-6-phosphate dehydrogenase (G6PD) activity In addition, types 1, 3, 4 (GLUT1, GLUT3, GLUT4), synthesis cytochrome c oxidase 2 expression along HUVECs. Exposure diminishes therapeutic potential MSC-derived disrupting energy promoting reprogramming cells. These findings suggest that adjusting dosage frequency may enhance their efficacy treating diabetes-related conditions. Further research warranted AGEs' broader various pathways improved exosome-based therapies.

Language: Английский

Effect of MSC-derived EVs induced by AGEs on energy metabolism in vascular endothelial cells DOI Creative Commons
Jiabin Liang,

Sihang Cheng,

Qi-De Song

et al.

Kidney International Reports, Journal Year: 2024, Volume and Issue: 10(1), P. 227 - 246

Published: Oct. 22, 2024

Advanced glycation end products (AGEs) play a critical role in the development of vascular diseases diabetes. Although stem cell therapies often involve exposure to AGEs, impact this environment on extracellular vesicles (EVs) and endothelial metabolism remains unclear. Human umbilical cord mesenchymal cells (MSCs) were treated with either 0 ng/ml or 100 AGEs serum-free medium for 48 hours, after which MSC-EVs isolated. The EVs characterized by morphology, particle size, protein markers MSC-EVs, microRNA (miRNA) sequencing was performed identify differentially expressed miRNAs. cocultured human vein (HUVECs) assess effects viability, metabolic activity, oxidative stress, antioxidant capacity. Tube formation glucose transporter analyses conducted evaluate angiogenic ability ranged from 30 150 nm, is consistent exosomal properties. treatment reduced MSC viability but had minimal effect EV morphology markers. miRNA showed downregulation hsa-miR-223-3p hsa-miR-126-3p_R-1, upregulation hsa-miR-574-5p, implicating changes glycolytic phosphorylation pathways. decreased HUVEC (P < 0.05), pH adenosine triphosphate (ATP) while enhancing glycolysis processes, including capacity, reserve 0.05). This likely resulted impaired mitochondrial function, ATP production, maximal respiration, basal spare respiratory capacity increased reactive oxygen species (ROS) 0.05) glucose-6-phosphate dehydrogenase (G6PD) activity In addition, types 1, 3, 4 (GLUT1, GLUT3, GLUT4), synthesis cytochrome c oxidase 2 expression along HUVECs. Exposure diminishes therapeutic potential MSC-derived disrupting energy promoting reprogramming cells. These findings suggest that adjusting dosage frequency may enhance their efficacy treating diabetes-related conditions. Further research warranted AGEs' broader various pathways improved exosome-based therapies.

Language: Английский

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