M1 Microglia-derived Exosomes Promote Activation of Resting Microglia and Amplifies Proangiogenic Effects through Irf1/miR-155-5p/Socs1 Axis in the Retina

Chen, Xi; Wang, Xiao; Cui, Zedu; Luo, Qian; Jiang, Zihua; Huang, Yuke; Jiang, Jingyi; Qiu, Jin; Li, Yan; Yu, Keming; Zhuang, Jing

doi:10.7150/ijbs.79784

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Int J Biol Sci 2023; 19(6):1791-1812. doi:10.7150/ijbs.79784 This issue Cite

Research Paper

M1 Microglia-derived Exosomes Promote Activation of Resting Microglia and Amplifies Proangiogenic Effects through Irf1/miR-155-5p/Socs1 Axis in the Retina

Xi Chen^1,2,3#, Xiao Wang^1,2,3#, Zedu Cui^1,2,3, Qian Luo^1,2,3, Zihua Jiang^1,2,3, Yuke Huang^1,2,3, Jingyi Jiang^1,2,3, Jin Qiu^1,2,3, Yan Li^1,2,3, Keming Yu^1,2,3✉, Jing Zhuang^1,2,3✉

1. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, No.7 Jinsui Road, Tianhe District, Guangzhou, 510060, China
2. Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, 510060, China
3. Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, 510060, China
# Xi Chen and Xiao Wang contributed equally as co-first authors.

Citation:

Chen X, Wang X, Cui Z, Luo Q, Jiang Z, Huang Y, Jiang J, Qiu J, Li Y, Yu K, Zhuang J. M1 Microglia-derived Exosomes Promote Activation of Resting Microglia and Amplifies Proangiogenic Effects through Irf1/miR-155-5p/Socs1 Axis in the Retina. Int J Biol Sci 2023; 19(6):1791-1812. doi:10.7150/ijbs.79784. https://www.ijbs.com/v19p1791.htm

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Abstract

Activation of microglia plays a key role in the development of neovascular retinal diseases. Therefore, it is essential to reveal its pathophysiological and molecular mechanisms to interfere with disease progression. Here a publicly available single-cell RNA sequencing dataset is used to identify that intercellular communications from M1 microglia toward M0 microglia are increased in the retinal angiogenesis model via exosomes. Moreover, the results both in vitro and in vivo demonstrate that M1 microglia-derived exosomes promote the activation and enhance the proangiogenic ability of resting microglia. Based on miRNA sequencing of exosomes combined with gene interference, further results show that activated microglia-derived exosomes promoted microglial activation by transmitting polarized signals to M0 microglia via miR-155-5p. Subsequently, miR-155-5p suppresses Socs1 and activates the NFκB pathway, which ultimately causes the inflammatory cascade and amplifies the proangiogenic effect. In addition, upregulated Irf1 drives the expression of miR-155-5p in activated microglia, thus leading to an increase in the tendency of miR-155-5p to be encapsulated by exosomes. Thus, this study elucidates the critical role of intercellular communication among various types of microglia in the complex retinal microenvironment during angiogenesis, and contributes to the novel, targeted, and potential therapeutic strategies for clinical retinal neovascularization.

Keywords: microglia, exosomes, inflammation, neovascularization, retina

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APA

Chen, X., Wang, X., Cui, Z., Luo, Q., Jiang, Z., Huang, Y., Jiang, J., Qiu, J., Li, Y., Yu, K., Zhuang, J. (2023). M1 Microglia-derived Exosomes Promote Activation of Resting Microglia and Amplifies Proangiogenic Effects through Irf1/miR-155-5p/Socs1 Axis in the Retina. International Journal of Biological Sciences, 19(6), 1791-1812. https://doi.org/10.7150/ijbs.79784.

ACS

Chen, X.; Wang, X.; Cui, Z.; Luo, Q.; Jiang, Z.; Huang, Y.; Jiang, J.; Qiu, J.; Li, Y.; Yu, K.; Zhuang, J. M1 Microglia-derived Exosomes Promote Activation of Resting Microglia and Amplifies Proangiogenic Effects through Irf1/miR-155-5p/Socs1 Axis in the Retina. Int. J. Biol. Sci. 2023, 19 (6), 1791-1812. DOI: 10.7150/ijbs.79784.

NLM

CSE

Chen X, Wang X, Cui Z, Luo Q, Jiang Z, Huang Y, Jiang J, Qiu J, Li Y, Yu K, Zhuang J. 2023. M1 Microglia-derived Exosomes Promote Activation of Resting Microglia and Amplifies Proangiogenic Effects through Irf1/miR-155-5p/Socs1 Axis in the Retina. Int J Biol Sci. 19(6):1791-1812.

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