Peripheral Macrophage-derived Exosomes promote repair after Spinal Cord Injury by inducing Local Anti-inflammatory type Microglial Polarization via Increasing Autophagy

• Published in: International journal of biological sciences Vol. 17; no. 5; pp. 1339 - 1352
• Main Authors: Zhang, Baokun, Lin, Fangqi, Dong, Jiqing, Liu, Jingwen, Ding, Zhenyu, Xu, Jianguang
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher Pty Ltd 01.01.2021; Ivyspring International Publisher
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Antibodies; Autophagy; Autophagy - immunology; Cell Polarity - physiology; Cell-Derived Microparticles - immunology; Cell-Derived Microparticles - metabolism; Cell-Derived Microparticles - transplantation; Chemical compounds; Contusions; Exosomes; Exosomes - immunology; Exosomes - metabolism; Exosomes - transplantation; In vivo methods and tests; Inflammation; Inflammation - metabolism; Inflammation - therapy; Laboratory animals; Macrophages; Macrophages - immunology; Microglia; Microglia - immunology; Microglia - metabolism; Phagocytosis; Pharmacology; Phosphatidylinositol 3-Kinases - metabolism; Polarization; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Sprague-Dawley; Reagents; Recovery of Function - physiology; Research Paper; Signal Transduction; Signal transmission; Signaling; Spinal cord injuries; Spinal Cord Injuries - immunology; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - therapy; TOR protein; TOR Serine-Threonine Kinases - metabolism; Treatment Outcome; United States > US; spinal cord injury; autophagy; peripheral macrophage; exosomes; microglia polarization
• ISSN: 1449-2288; 1449-2288
• DOI: 10.7150/ijbs.54302

Treatment for spinal cord injury (SCI) remains a challenge worldwide, and inflammation is a major cause of secondary injury after SCI. Peripheral macrophages (PMs) have been verified as a key factor that exert anti-inflammatory effects after SCI, but the mechanism is unidentified. As local macrophages, microglia also exert significant effects after SCI, especially polarization. Exosomes show source cell-like biological functions to target cells and have been the subject of much research in recent years. Thus, we hypothesized the PM-derived exosomes (PM-Exos) play an important role in signal transmission with local microglia and can be used therapeutic agents for SCI in a series of and studies. For the experiment, three groups of Sprague-Dawley (SD) rats subjected to spinal cord contusion injury were injected with 200 µg/ml PM-Exos, 20 µg/ml PM-Exos or PBS via the tail vein. Recovery of the rats and of spinal cord function were observed. , we investigated the potential anti-inflammatory mechanism of PM-Exos and evaluated microglial autophagy, anti-inflammatory type microglia polarization and the upstream signaling pathway. The results showed that spinal cord function and recovery were better in the PM-Exo groups than the control group. In the study, microglial autophagy levels and the expression of anti-inflammatory type microglia were higher in the experimental groups than the control group. Moreover, the expression of proteins related to the PI3K/AKT/mTOR autophagic signaling pathway was suppressed in the PM-Exo groups. PM-Exos have a beneficial effect in SCI, and activation of microglial autophagy via inhibition of the PI3K/AKT/mTOR signaling pathway, enhancing the polarization of anti-inflammatory type microglia, that may play a major role in the anti-inflammatory process.