胞外囊泡在皮肤科的研究进展和应用前景

doi:10.35541/cjd.20191072

摘要/Abstract

摘要： 【摘要】胞外囊泡是由细胞分泌的纳米级囊泡，包括外泌体和微囊泡。它可以通过多种机制被受体细胞摄取，传递细胞间信息，调控细胞的生物学功能。有研究发现，胞外囊泡与自身免疫性疾病、色素性疾病、肿瘤及皮肤创伤愈合等密切相关，在各种生理和病理过程中发挥着重要的生物学作用。本文综述胞外囊泡与皮肤科相关研究进展。

关键词: 外泌体, 胞外囊泡, 微囊泡, 皮肤疾病

Abstract: 【Abstract】 Extracellular vesicles are nanoscale vesicles secreted by cells, including exosomes and microvesicles. They can be ingested by recipient cells through a variety of mechanisms, transmitting intercellular information and regulating biological functions of recipient cells. Studies have found that extracellular vesicles are closely related to skin diseases, such as autoimmune diseases, pigmented diseases, tumors and wound healing, and play important biological roles in various physiological and pathological processes. This review summarizes updates on extracellular vesicles in dermatology.

Key words: Exosomes, Extracellular vesicles, Microvesicles, Skin diseases

陈伟谢恒李利. 胞外囊泡在皮肤科的研究进展和应用前景[J]. 中华皮肤科杂志, 2021, 54(10): 910-914.doi:10.35541/cjd.20191072

Chen Wei, Xie Heng, Li Li. Extracellular vesicles in dermatology: updates and prospects[J]. Chinese Journal of Dermatology, 2021, 54(10): 910-914.doi:10.35541/cjd.20191072

参考文献 53

［1］	Jurj A, Zanoaga O, Braicu C, et al. A comprehensive picture of extracellular vesicles and their contents. molecular transfer to cancer cells［J］. Cancers, 2020,12（2）.pii:E298. doi: 10.3390/cancers12020298.
［2］	van Niel G, D′Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles［J］. Nat Rev Mol Cell Biol, 2018,19（4）:213⁃228. doi: 10.1038/nrm.2017.125.
［3］	Riazifar M, Pone EJ, Lötvall J, et al. Stem cell extracellular vesicles: extended messages of regeneration［J］. Annu Rev Pharmacol Toxicol, 2017,57:125⁃154. doi: 10.1146/annurev⁃pharmtox⁃061616⁃030146.
［4］	Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends［J］. J Cell Biol, 2013,200（4）:373⁃383. doi: 10.1083/jcb.201211138.
［5］	Xu R, Greening DW, Zhu HJ, et al. Extracellular vesicle isolation and characterization: toward clinical application［J］. J Clin Invest, 2016,126（4）:1152⁃1162. doi: 10.1172/JCI81129.
［6］	Kotzerke K, Mempel M, Aung T, et al. Immunostimulatory activity of murine keratinocyte⁃derived exosomes［J］. Exp Dermatol, 2013,22（10）:650⁃655. doi: 10.1111/exd.12230.
［7］	Cai XW, Zhu R, Ran L, et al. A novel non⁃contact communication between human keratinocytes and T cells: exosomes derived from keratinocytes support superantigen⁃induced proliferation of resting T cells［J］. Mol Med Rep, 2017,16（5）:7032⁃7038. doi: 10.3892/mmr.2017.7492.
［8］	Medina A, Ghahary A. Transdifferentiated circulating monocytes release exosomes containing 14⁃3⁃3 proteins with matrix metalloproteinase⁃1 stimulating effect for dermal fibroblasts［J］. Wound Repair Regen, 2010,18（2）:245⁃253. doi: 10.1111/j.1524⁃ 475X.2010.00580.x.
［9］	Shefler I, Pasmanik⁃Chor M, Kidron D, et al. T cell⁃derived microvesicles induce mast cell production of IL⁃24: relevance to inflammatory skin diseases［J］. J Allergy Clin Immunol, 2014,133（1）:217⁃224.e1⁃3. doi: 10.1016/j.jaci.2013.04.035.
［10］	López P, Rodríguez⁃Carrio J, Martínez⁃Zapico A, et al. Circulating microparticle subpopulations in systemic lupus erythematosus are affected by disease activity［J］. Int J Cardiol, 2017,236:138⁃144. doi: 10.1016/j.ijcard.2017.02.107.
［11］	Ulivieri C, Baldari CT. Regulation of T cell activation and differentiation by extracellular vesicles and their pathogenic role in systemic lupus erythematosus and multiple sclerosis［J］. Molecules, 2017,22（2）. pii:E225. doi: 10.3390/molecules2202 0225.
［12］	Nielsen CT, Østergaard O, Rekvig OP, et al. Galectin⁃3 binding protein links circulating microparticles with electron dense glomerular deposits in lupus nephritis［J］. Lupus, 2015,24（11）:1150⁃1160. doi: 10.1177/0961203315580146.
［13］	张淑娟, 唐亚萍, 梁景耀, 等. 姜黄素逆转系统性红斑狼疮患者外泌体诱导的巨噬细胞吞噬功能受损［J］. 中华皮肤科杂志, 2019,52（6）:378⁃382. doi: 10.3760/cma.j.issn.0412⁃4030. 2019.06.002.
［14］	Fang H, Shao S, Jiang M, et al. Proinflammatory role of blister fluid⁃derived exosomes in bullous pemphigoid［J］. J Pathol, 2018,245（1）:114⁃125. doi: 10.1002/path.5061.
［15］	Cheung KL, Jarrett R, Subramaniam S, et al. Psoriatic T cells recognize neolipid antigens generated by mast cell phospholipase delivered by exosomes and presented by CD1a［J］. J Exp Med, 2016,213（11）:2399⁃2412. doi: 10.1084/jem. 20160258.
［16］	Pelletier F, Garnache⁃Ottou F, Biichlé S, et al. Effects of anti⁃TNF⁃α agents on circulating endothelial⁃derived and platelet⁃derived microparticles in psoriasis［J］. Exp Dermatol, 2014,23（12）:924⁃925. doi: 10.1111/exd.12551.
［17］	Schorey JS, Harding CV. Extracellular vesicles and infectious diseases: new complexity to an old story［J］. J Clin Invest, 2016,126（4）:1181⁃1189. doi: 10.1172/JCI81132.
［18］	Gehrmann U, Qazi KR, Johansson C, et al. Nanovesicles from Malassezia sympodialis and host exosomes induce cytokine responses⁃⁃novel mechanisms for host⁃microbe interactions in atopic eczema［J/OL］. PLoS One, 2011,6（7）:e21480. doi: 10.1371/journal.pone.0021480.
［19］	Jun SH, Lee JH, Kim SI, et al. Staphylococcus aureus⁃derived membrane vesicles exacerbate skin inflammation in atopic dermatitis［J］. Clin Exp Allergy, 2017,47（1）:85⁃96. doi: 10. 1111/cea.12851.
［20］	Kim YS, Choi EJ, Lee WH, et al. Extracellular vesicles, especially derived from Gram⁃negative bacteria, in indoor dust induce neutrophilic pulmonary inflammation associated with both Th1 and Th17 cell responses［J］. Clin Exp Allergy, 2013,43（4）:443⁃454. doi: 10.1111/cea.12085.
［21］	Choi EJ, Lee HG, Bae IH, et al. Propionibacterium acnes⁃derived extracellular vesicles promote acne⁃like phenotypes in human epidermis［J］. J Invest Dermatol, 2018,138（6）:1371⁃1379. doi: 10.1016/j.jid.2018.01.007.
［22］	许卜方, 王千秋, 张瑞丽, 等. 梅毒螺旋体诱导巨噬细胞分泌的外泌体特征及其对人脐静脉内皮细胞增殖的影响［J］. 中华皮肤科杂志, 2018,51（5）:341⁃346. doi: 10.3760/cma.j.issn. 0412⁃4030.2018.05.005.
［23］	Mercier SK, Donaghy H, Botting RA, et al. The microvesicle component of HIV⁃1 inocula modulates dendritic cell infection and maturation and enhances adhesion to and activation of T lymphocytes［J/OL］. PLoS Pathog, 2013,9（10）:e1003700. doi: 10. 1371/journal.ppat.1003700.
［24］	Ñahui Palomino RA, Vanpouille C, Laghi L, et al. Extracellular vesicles from symbiotic vaginal lactobacilli inhibit HIV⁃1 infection of human tissues［J］. Nat Commun, 2019,10（1）:5656. doi: 10.1038/s41467⁃019⁃13468⁃9.
［25］	Lo Cicero A, Delevoye C, Gilles⁃Marsens F, et al. Exosomes released by keratinocytes modulate melanocyte pigmentation［J］. Nat Commun, 2015,6:7506. doi: 10.1038/ncomms8506.
［26］	Kim NH, Choi SH, Kim CH, et al. Reduced miR⁃675 in exosome in H19 RNA⁃related melanogenesis via MITF as a direct target［J］. J Invest Dermatol, 2014,134（4）:1075⁃1082. doi: 10.1038/jid.2013.478.
［27］	Wäster P, Eriksson I, Vainikka L, et al. Extracellular vesicles are transferred from melanocytes to keratinocytes after UVA irradiation［J］. Sci Rep, 2016,6:27890. doi: 10.1038/srep27890.
［28］	Bin BH, Kim DK, Kim NH, et al. Fibronectin⁃containing extracellular vesicles protect melanocytes against ultraviolet radiation⁃induced cytotoxicity［J］. J Invest Dermatol, 2016,136（5）:957⁃966. doi: 10.1016/j.jid.2015.08.001.
［29］	Peinado H, Alečković M, Lavotshkin S, et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro⁃metastatic phenotype through MET［J］. Nat Med, 2012,18（6）:883⁃891. doi: 10.1038/nm.2753.
［30］	Romano G, Kwong LN. MiRNAs, melanoma and microenvironment: an intricate network［J］. Int J Mol Sci, 2017,18（11）. pii: E2354. doi: 10.3390/ijms18112354.
［31］	Tucci M, Passarelli A, Mannavola F, et al. Serum exosomes as predictors of clinical response to ipilimumab in metastatic melanoma［J］. Oncoimmunology, 2018,7（2）:e1387706. doi: 10.1080/2162402X.2017.1387706.
［32］	王江文,易阳艳,朱元正,等. 脂肪干细胞来源外泌体促进糖尿病小鼠创面愈合的实验研究［J］. 中国修复重建外科杂志, 2020,34（1）:124⁃131. doi: 10.7507/1002⁃1892.201903058.
［33］	陈涛, 高绍莹, 郝艺, 等. 人羊膜间充质干细胞外泌体通过miR⁃135a促进成纤维细胞迁移实验研究［J］. 中国修复重建外科杂志, 2020,34（2）:234⁃239. doi: 10.7507/1002⁃1892.20 1907136.
［34］	李全, 崔凤瑞, 巴特, 等. 脂肪干细胞来源的外泌体促进肉芽组织来源的成纤维细胞增殖的初步研究［J］. 中华损伤与修复杂志（电子版）, 2019,14（2）:91⁃96. doi: 10.3877/cma.j.issn. 1673⁃9450.2019.02.003.
［35］	张远远, 曾悦, 朱艳霞, 等. 人脂肪干细胞源外泌体对HaCaT细胞损伤修复及迁移功能影响的初步实验研究［J］. 中华皮肤科杂志, 2019,52（9）:616⁃623. doi: 10.3760/cma.j.issn.0412⁃4030.2019.09.006.
［36］	田新立, 江波, 颜洪. 脂肪间充质干细胞来源外泌体对角质形成细胞增殖和迁移的影响与机制［J］. 中国组织工程研究, 2019,23（1）:68⁃73. doi: 10.3969/j.issn.2095⁃4344.1527.
［37］	Beer L, Zimmermann M, Mitterbauer A, et al. Analysis of the secretome of apoptotic peripheral blood mononuclear cells: impact of released proteins and exosomes for tissue regeneration［J］. Sci Rep, 2015,5:16662. doi: 10.1038/srep16662.
［38］	McBride JD, Rodriguez⁃Menocal L, Badiavas EV. Extracellular vesicles as biomarkers and therapeutics in dermatology: a focus on exosomes［J］. J Invest Dermatol, 2017,137（8）:1622⁃1629. doi: 10.1016/j.jid.2017.04.021.
［39］	Ferreira A, Cunha P, Carregal VM, et al. Extracellular vesicles from adipose⁃derived mesenchymal stem/stromal cells accelerate migration and activate AKT pathway in human keratinocytes and fibroblasts independently of miR⁃205 activity［J］. Stem Cells Int, 2017,2017:9841035. doi: 10.1155/2017/9841035.
［40］	Than U, Guanzon D, Leavesley D, et al. Association of extracellular membrane vesicles with cutaneous wound healing［J］. Int J Mol Sci, 2017,18（5）. pii: E956. doi: 10.3390/ijms1805 0956.
［41］	Li Q, Zhao H, Chen W, et al. Human keratinocyte⁃derived microvesicle miRNA⁃21 promotes skin wound healing in diabetic rats through facilitating fibroblast function and angiogenesis［J］. Int J Biochem Cell Biol, 2019,114:105570. doi: 10.1016/j.biocel.2019.105570.
［42］	Del Re M, Marconcini R, Pasquini G, et al. PD⁃L1 mRNA expression in plasma⁃derived exosomes is associated with response to anti⁃PD⁃1 antibodies in melanoma and NSCLC［J］. Br J Cancer, 2018,118（6）:820⁃824. doi: 10.1038/bjc.2018.9.
［43］	Cordonnier M, Nardin C, Chanteloup G, et al. Tracking the evolution of circulating exosomal⁃PD⁃L1 to monitor melanoma patients［J］. J Extracell Vesicles, 2020,9（1）:1710899. doi: 10. 1080/20013078.2019.1710899.
［44］	Svedman FC, Lohcharoenkal W, Bottai M, et al. Extracellular microvesicle microRNAs as predictive biomarkers for targeted therapy in metastastic cutaneous malignant melanoma［J/OL］. PLoS One, 2018,13（11）:e0206942. doi: 10.1371/journal.pone. 0206942.
［45］	Theodoraki MN, Yerneni SS, Hoffmann TK, et al. Clinical significance of PD⁃L1+ exosomes in plasma of head and neck cancer patients［J］. Clin Cancer Res, 2018,24（4）:896⁃905. doi: 10.1158/1078⁃0432.CCR⁃17⁃2664.
［46］	Dong C, Zhou Q, Fu T, et al. Circulating exosomes derived⁃miR⁃146a from systemic lupus erythematosus patients regulates senescence of mesenchymal stem cells［J］. Biomed Res Int, 2019,2019:6071308. doi: 10.1155/2019/6071308.
［47］	Lu J, Hu ZB, Chen PP, et al. Urinary podocyte microparticles are associated with disease activity and renal injury in systemic lupus erythematosus［J］. BMC Nephrol, 2019,20（1）:303. doi: 10.1186/s12882⁃019⁃1482⁃z.
［48］	Tangtanatakul P, Klinchanhom S, Sodsai P, et al. Down⁃regulation of let⁃7a and miR⁃21 in urine exosomes from lupus nephritis patients during disease flare［J］. Asian Pac J Allergy Immunol, 2019,37（4）:189⁃197. doi: 10.12932/AP⁃130318⁃0280.
［49］	Perez⁃Hernandez J, Redon J, Cortes R. Extracellular vesicles as therapeutic agents in systemic lupus erythematosus［J］. Int J Mol Sci, 2017,18（4）. pii: E717. doi: 10.3390/ijms18040717.
［50］	Chen C, Wang D, Moshaverinia A, et al. Mesenchymal stem cell transplantation in tight⁃skin mice identifies miR⁃151⁃5p as a therapeutic target for systemic sclerosis［J］. Cell Res, 2017,27（4）:559⁃577. doi: 10.1038/cr.2017.11.
［51］	Du YM, Zhuansun YX, Chen R, et al. Mesenchymal stem cell exosomes promote immunosuppression of regulatory T cells in asthma［J］. Exp Cell Res, 2018,363（1）:114⁃120. doi: 10.1016/j.yexcr.2017.12.021.
［52］	Pitt JM, André F, Amigorena S, et al. Dendritic cell⁃derived exosomes for cancer therapy［J］. J Clin Invest, 2016,126（4）:1224⁃1232. doi: 10.1172/JCI81137.
［53］	Zhu L, Kalimuthu S, Gangadaran P, et al. Exosomes derived from natural killer cells exert therapeutic effect in melanoma［J］. Theranostics, 2017,7（10）:2732⁃2745. doi: 10.7150/thno. 18752.

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