Exosomes, as key tools of cellular communication, are involved in both physiological processes and pathological development of the organism.Macrophages are an important component of the body's intrinsic immunity and play an important role in the regulation of inflammation, maintenance of intra-tissue stability, and promotion of tissue repair and regeneration.Under the regulation of exosomal signaling, macrophages can polarize into M1-type pro-inflammatory and anti-tumor subtypes and M2-type anti-inflammatory and pro-tumor subtypes, which play a double-edged role in the development and progression of disease.This paper discusses the ways and pathways of exosomal micro-molecular long-stranded non-coding RNAs and miRNAs of different cellular origins affecting macrophage polarization and phenotype in three areas: tumor, neurological diseases, and cardiovascular diseases, aiming to provide new ideas and methods for research in this field.

Sansan Li, Yindi Wang, Zhen Lv, Mingyu Zhang, Jianjun Wu, DongJin Ma. Research on the Effect of Exosomes on the Polarization of Macrophages. International Journal of Frontiers in Medicine (2022), Vol. 4, Issue 11: 31-36. https://doi.org/10.25236/IJFM.2022.041105.

[1] PAN B T, JOHNSTONE R M. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor [J]. Cell, 1983, 33(3): 967-978.

[2] Zhang S, Ni X. Lu L. Research progress of exosomes and their effects on regulatory T cells [J] Chinese Journal of Immunology, 2018, 34 (03): 450-459.

[3] HUANG L, MA W, MA Y, et al. Exosomes in mesenchymal stem cells, a new therapeutic strategy for cardiovascular diseases? [J]. International journal of biological sciences, 2015, 11(2): 238-245.

[4] ZHANG B, WANG M, GONG A, et al. HucMSC-Exosome Mediated-Wnt4 Signaling Is Required for Cutaneous Wound Healing [J]. Stem cells (Dayton, Ohio), 2015, 33(7): 2158-2168.

[5] ZHANG S, CHUAH S J, LAI R C, et al. MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity [J]. Biomaterials, 2018, 156: 16-27.

[6] HAN C, SUN X, LIU L, et al. Exosomes and Their Therapeutic Potentials of Stem Cells [J]. Stem cells international, 2016, 2016: 765-775.

[7] LOU G, CHEN Z, ZHENG M, et al. Mesenchymal stem cell-derived exosomes as a new therapeutic strategy for liver diseases [J]. Experimental & molecular medicine, 2017, 49(6): e346.

[8] ANDRE F, SCHARTZ N E, MOVASSAGH M, et al. Malignant effusions and immunogenic tumour-derived exosomes [J]. Lancet (London, England), 2002, 360(9329): 295-305.

[9] ESSANDOH K, LI Y, HUO J, et al. MiRNA-Mediated Macrophage Polarization and its Potential Role in the Regulation of Inflammatory Response [J]. Shock (Augusta, Ga), 2016, 46(2): 122-131.

[10] Ding H, Li L, Zhang D, et al. Research progress on the role of tumor associated macrophages in tumor progression and treatment strategies [J]. Journal of Clinical and Experimental Pathology, 2020, 36 (07): 812-815.

[11] Zhou A, Tan Y, Zhang H. Regulation of TLR4/NF by lncRNA CASC11 in gastric cancer exocrine cells- κ B pathway induces polarization of M2 type macrophages [J]. Hebei Medical Journal, 2021, 27 (12): 1948-1957.

[12] Zhang X, Wu D, Zhang X, et al. Study on the polarization function and mechanism of M2 macrophages induced by gastric cancer exocrine lncRNA LOXL1-AS1 [J]. Modern Tumor Medicine, 2022,30 (08): 1374-1380.

[13] XIN L, WU Y, LIU C, et al. Exosome-mediated transfer of lncRNA HCG18 promotes M2 macrophage polarization in gastric cancer [J]. Molecular immunology, 2021, 140: 196-205.

[14] LIU S Q, ZHOU Z Y, DONG X, et al. LncRNA GNAS-AS1 facilitates ER+ breast cancer cells progression by promoting M2 macrophage polarization via regulating miR-433-3p/GATA3 axis [J]. Bioscience reports, 2020, 40(7): 1324-1336.

[15] LIANG Y, SONG X, LI Y, et al. LncRNA BCRT1 promotes breast cancer progression by targeting miR-1303/PTBP3 axis [J]. Molecular cancer, 2020, 19(1): 85-96.

[16] ZONG S, DAI W, GUO X, et al. LncRNA-SNHG1 promotes macrophage M2-like polarization and contributes to breast cancer growth and metastasis [J]. Aging, 2021, 13(19): 23169-23181.

[17] ZHOU L, TIAN Y, GUO F, et al. LincRNA-p21 knockdown reversed tumor-associated macrophages function by promoting MDM2 to antagonize* p53 activation and alleviate breast cancer development [J]. Cancer immunology, immunotherapy: CII, 2020, 69(5): 835-846.

[18] LIU Q, YU W, ZHU S, et al. Long noncoding RNA GAS5 regulates the proliferation, migration, and invasion of glioma cells by negatively regulating miR-18a-5p [J]. Journal of cellular physiology, 2018, 234(1): 757-768.

[19] CHI X, DING B, ZHANG L, et al. lncRNA GAS5 promotes M1 macrophage polarization via miR-455-5p/SOCS3 pathway in childhood pneumonia [J]. Journal of cellular physiology, 2019, 234(8): 13242-13251.

[20] CAO J, DONG R, JIANG L, et al. LncRNA-MM2P Identified as a Modulator of Macrophage M2 Polarization [J]. Cancer immunology research, 2019, 7(2): 292-305.

[21] Cai X, Yi X, Yao J, et al. Exosomes secreted by human bone marrow mesenchymal stem cells regulate the polarization of malignant glioma associated macrophages [J]. Journal of Kunming Medical University, 2021, 42 (01): 38-45.

[22] COLONNA M, BUTOVSKY O. Microglia Function in the Central Nervous System during Health and Neurodegeneration [J]. Annual review of immunology, 2017, 35: 441-468.

[23] YOUNG D A, LOWE L D, CLARK S C. Comparison of the effects of IL-3, granulocyte-macrophage colony-stimulating factor, and macrophage colony-stimulating factor in supporting monocyte differentiation in culture. Analysis of macrophage antibody-dependent cellular cytotoxicity [J]. Journal of immunology (Baltimore, Md: 1950), 1990, 145(2): 607-615.

[24] PENG P, ZHANG B, HUANG J, et al. Identification of a circRNA-miRNA-mRNA network to explore the effects of circRNAs on pathogenesis and treatment of spinal cord injury [J]. Life Sci, 2020, 257: 118-129.

[25] LI R, ZHAO K, RUAN Q, et al. Bone marrow mesenchymal stem cell-derived exosomal microRNA-124-3p attenuates neurological damage in spinal cord ischemia-reperfusion injury by downregulating Ern1 and promoting M2 macrophage polarization [J]. Arthritis research & therapy, 2020, 22(1): 75-81.

[26] ZHANG M, WANG L, HUANG S, et al. Exosomes with high level of miR-181c from bone marrow-derived mesenchymal stem cells inhibit inflammation and apoptosis to alleviate spinal cord injury [J]. Journal of molecular histology, 2021, 52(2): 301-311.

[27] YANG C, CHEN C, XIAO Q, et al. Relationship between PTEN and Angiogenesis of Esophageal Squamous Cell Carcinoma and the Underlying Mechanism [J]. Frontiers in oncology, 2021, 11: 739-741.

[28] CHOW J T, SALMENA L. Recent advances in PTEN signalling axes in cancer [J]. Faculty reviews, 2020, 9: 31-41.

[29] LIU W, RONG Y, WANG J, et al. Exosome-shuttled miR-216a-5p from hypoxic preconditioned mesenchymal stem cells repair traumatic spinal cord injury by shifting microglial M1/M2 polarization [J]. Journal of neuroinflammation, 2020, 17(1): 47-60.

[30] FANG H, YANG M, PAN Q, et al. MicroRNA-22-3p alleviates spinal cord ischemia/reperfusion injury by modulating M2 macrophage polarization via IRF5 [J]. Journal of neurochemistry, 2021, 156(1): 106-120.

[31] CHANG Q, HAO Y, WANG Y, et al. Bone marrow mesenchymal stem cell-derived exosomal microRNA-125a promotes M2 macrophage polarization in spinal cord injury by downregulating IRF5 [J]. Brain Research Bulletin, 2021, 170: 199-210.

[32] Key points of China Cardiovascular Health and Disease Report 2020 [J]. Chinese Journal of Cardiology, 2021, 26 (03): 209218.

[33] DENG S, ZHOU X, GE Z, et al. Exosomes from adipose-derived mesenchymal stem cells ameliorate cardiac damage after myocardial infarction by activating S1P/SK1/S1PR1 signaling and promoting macrophage M2 polarization [J]. The international journal of biochemistry & cell biology, 2019, 114: 105-117.

[34] XU R, ZHANG F, CHAI R, et al. Exosomes derived from pro-inflammatory bone marrow-derived mesenchymal stem cells reduce inflammation and myocardial injury via mediating macrophage polarization [J]. Journal of cellular and molecular medicine, 2019, 23(11): 7617-7631.

[35] Zhao J. Study on the effect and mechanism of mesenchymal stem cell exosomes on macrophage polarization after myocardial ischemia/reperfusion [D]; Nanjing: Nanjing University, 2019.

[36] ZHAO J, LI X, HU J, et al. Mesenchymal stromal cell-derived exosomes attenuate myocardial ischaemia-reperfusion injury through miR-182-regulated macrophage polarization [J]. Cardiovascular research, 2019, 115(7): 1205-1216.

[37] SHEN D, HE Z. Mesenchymal stem cell-derived exosomes regulate the polarization and inflammatory response of macrophages via miR-21-5p to promote repair after myocardial reperfusion injury [J]. Annals of translational medicine, 2021, 9(16): 1323-1334.

[38] MA J, CHEN L, ZHU X, et al. Mesenchymal stem cell-derived exosomal miR-21a-5p promotes M2 macrophage polarization and reduces macrophage infiltration to attenuate atherosclerosis [J]. Acta biochimica et biophysica Sinica, 2021, 53(9): 1227-1236.

[39] LI J, XUE H, LI T, et al. Exosomes derived from mesenchymal stem cells attenuate the progression of atherosclerosis in ApoE(-/-) mice via miR-let7 mediated infiltration and polarization of M2 macrophage [J]. Biochemical and biophysical research communications, 2019, 510(4): 565-572.

[40] Bi J, Zeng X, Wei M, et al.[] Research progress in the regulation of macrophage polarization by microRNA [J]. Journal of Cell and Molecular Immunology, 2015, 31 (11): 1560-1576.