Figure 4.

Exosomes are involved in the disease progression of DPN. miR-21-5p carried by DRG neurons-Exo increases TNF-α, IL-6 and other inflammatory factors, inducing inflammatory reactions. miR-146a carried by BM-MSCs-Exo also increases TNF-α, mediating the inflammatory reaction. The increases in miR-28, -31a and -130a in Schwann cells-Exo target DNMT-3A, NUMB, SNAP-25 and GAP-43, which causes axon ischemia, hypoxia and abnormal metabolism and inhibits axon growth. BM-MSCs-Exo carry let-7a, miR-17, miR-23 and other molecules that target the TLR4/NF-κB signaling pathway, which leads to a decrease in neurotrophic factors. Under high glucose conditions, part of the reason for the damage to the nervous system is the disturbance of nervous system homeostasis caused by oxidative stress and increased apoptosis. AS-Exos activate ROS and target the Ras/AMPK signaling pathway, causing mitochondrial dysfunction and apoptosis. DPN, diabetic peripheral neuropathy; BM-MSCs-Exo, exosomes derived from bone marrow mesenchymal stem cells; ROS, reactive oxygen species; miR, microRNA; DRG, dorsal root ganglia; DNMT-3A, DNA methyltransferase 3A; SNAP-25, synaptosome protein 25; GRP-43, growth-associated protein 43; AS, astrocytes; AMPK, adenosine monophosphate-activated protein kinase.