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Skeletal muscle‐derived exosomes regulate endothelial cell functions via reactive oxygen species‐activated nuclear factor‐κB signalling
- Source :
- Experimental Physiology. 104:1262-1273
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- New findings What is the central question of this study? Capillary rarefaction is found in diabetic and aged muscle, whereas exercise increases skeletal muscle angiogenesis. The association implies a crosstalk between muscle cells and endothelial cells. The underlying mechanisms mediating the crosstalk between these cells remains to be elucidated fully. What is the main finding and its importance? Endothelial cell functions are regulated by skeletal muscle cell-derived exosomes via a vascular endothelial growth factor-independent pathway. This study reveals a new mechanism mediating the crosstalk between skeletal muscle cells and endothelial cells. Abstract Loss of skeletal muscle capillarization, known as capillary rarefaction, is found in type 2 diabetes, chronic heart failure and healthy ageing and is associated with impaired delivery of substrates to the muscle. However, the interaction and communication of skeletal muscle with endothelial cells in the regulation of capillaries surrounding the muscle remains elusive. Exosomes are a type of secreted extracellular vesicle containing mRNAs, proteins and, especially, microRNAs that exert paracrine and endocrine effects. In this study, we investigated whether skeletal muscle-derived exosomes (SkM-Exo) regulate the endothelial cell functions of angiogenesis. We demonstrated that C2C12 myotube-derived exosomes improved endothelial cell functions, assessed by the proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs), which were increased by 20, 23 and 40%, respectively, after SkM-Exo exposure. The SkM-Exo failed to activate HUVEC vascular endothelial growth factor (VEGF) signalling. The SkM-Exo increased HUVEC reactive oxygen species and activated the nuclear factor-κB pathway, suggesting that SkM-Exo-induced angiogenesis was mediated by a VEGF-independent pathway. In addition, several angiogenic microRNAs were packaged in SkM-Exo, with miR-130a being particularly enriched and successfully transferred from SkM-Exo to HUVECs. Delivery of miRNAs into endothelial cells might explain the enhancement of reactive oxygen species production and angiogenesis by SkM-Exo. The potential angiogenic effect of SkM-Exo could provide an effective therapy for promoting skeletal muscle angiogenesis in diseases characterized by capillary rarefaction or inadequate angiogenesis.
- Subjects :
- Male
Vascular Endothelial Growth Factor A
Physiology
Angiogenesis
Muscle Fibers, Skeletal
Neovascularization, Physiologic
030204 cardiovascular system & hematology
Exosomes
Exosome
Cell Line
Mice
03 medical and health sciences
Paracrine signalling
chemistry.chemical_compound
0302 clinical medicine
Cell Movement
Physiology (medical)
Human Umbilical Vein Endothelial Cells
medicine
Animals
Humans
Myocyte
Muscle, Skeletal
Cell Proliferation
Nutrition and Dietetics
NF-kappa B
Skeletal muscle
Mesenchymal Stem Cells
General Medicine
Microvesicles
Cell biology
Mice, Inbred C57BL
Vascular endothelial growth factor
Endothelial stem cell
MicroRNAs
medicine.anatomical_structure
Diabetes Mellitus, Type 2
chemistry
Reactive Oxygen Species
030217 neurology & neurosurgery
Signal Transduction
Subjects
Details
- ISSN :
- 1469445X and 09580670
- Volume :
- 104
- Database :
- OpenAIRE
- Journal :
- Experimental Physiology
- Accession number :
- edsair.doi.dedup.....60d51adca16c2ee15b55d4876aa2fff6