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

Zhang, Baokun; Lin, Fangqi; Dong, Jiqing; Liu, Jingwen; Ding, Zhenyu; Xu, Jianguang

doi:10.7150/ijbs.54302

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Int J Biol Sci 2021; 17(5):1339-1352. doi:10.7150/ijbs.54302 This issue Cite

Research Paper

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

Baokun Zhang^1#, Fangqi Lin^1#, Jiqing Dong², Jingwen Liu¹, Zhenyu Ding¹, Jianguang Xu^1✉

1. Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated No. 6 People's Hospital, 600 Yishan Road, Shanghai 200233, China.
2. Department of Orthopedic Surgery,Rizhao Hospital of Traditional Chinese Medicine.
#These authors contributed equally to this work.

Citation:

Zhang B, Lin F, Dong J, Liu J, Ding Z, Xu J. Peripheral Macrophage-derived Exosomes promote repair after Spinal Cord Injury by inducing Local Anti-inflammatory type Microglial Polarization via Increasing Autophagy. Int J Biol Sci 2021; 17(5):1339-1352. doi:10.7150/ijbs.54302. https://www.ijbs.com/v17p1339.htm

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Abstract

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 in vivo and in vitro studies. For the in vivo 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. In vitro, 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 in vitro 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.

Keywords: spinal cord injury, peripheral macrophage, exosomes, microglia polarization, autophagy

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APA

Zhang, B., Lin, F., Dong, J., Liu, J., Ding, Z., Xu, J. (2021). Peripheral Macrophage-derived Exosomes promote repair after Spinal Cord Injury by inducing Local Anti-inflammatory type Microglial Polarization via Increasing Autophagy. International Journal of Biological Sciences, 17(5), 1339-1352. https://doi.org/10.7150/ijbs.54302.

ACS

Zhang, B.; Lin, F.; Dong, J.; Liu, J.; Ding, Z.; Xu, J. Peripheral Macrophage-derived Exosomes promote repair after Spinal Cord Injury by inducing Local Anti-inflammatory type Microglial Polarization via Increasing Autophagy. Int. J. Biol. Sci. 2021, 17 (5), 1339-1352. DOI: 10.7150/ijbs.54302.

NLM

CSE

Zhang B, Lin F, Dong J, Liu J, Ding Z, Xu J. 2021. Peripheral Macrophage-derived Exosomes promote repair after Spinal Cord Injury by inducing Local Anti-inflammatory type Microglial Polarization via Increasing Autophagy. Int J Biol Sci. 17(5):1339-1352.

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