Int J Biol Sci
2023; 19(6):1791-1812.
doi:10.7150/ijbs.79784 This issueCite
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 Chen1,2,3#, Xiao Wang1,2,3#, Zedu Cui1,2,3, Qian Luo1,2,3, Zihua Jiang1,2,3, Yuke Huang1,2,3, Jingyi Jiang1,2,3, Jin Qiu1,2,3, Yan Li1,2,3, Keming Yu1,2,3✉, Jing Zhuang1,2,3✉
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.
✉ Corresponding authors: Jing Zhuang (zhuangjsysu.edu.cn), and Keming Yu (yukemingsysu.edu.cn)
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
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.
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
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
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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