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Role of exosome-associated microRNA in diagnostic and therapeutic applications to metabolic disorders

外泌体相关的microRNA 在代谢性疾病诊断和治疗中的作用

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Abstract

Metabolic disorders are classified clinically as a complex and varied group of diseases including metabolic syndrome, obesity, and diabetes mellitus. Fat toxicity, chronic inflammation, and oxidative stress, which may change cellular functions, are considered to play an essential role in the pathogenetic progress of metabolic disorders. Recent studies have found that cells secrete nanoscale vesicles containing proteins, lipids, nucleic acids, and membrane receptors, which mediate signal transduction and material transport to neighboring and distant cells. Exosomes, one type of such vesicles, are reported to participate in multiple pathological processes including tumor metastasis, atherosclerosis, chronic inflammation, and insulin resistance. Research on exosomes has focused mainly on the proteins they contain, but recently the function of exosome-associated microRNA has drawn a lot of attention. Exosomeassociated microRNAs regulate the physiological function and pathological processes of metabolic disorders. They may also be useful as novel diagnostics and therapeutics given their special features of non-immunogenicity and quick extraction. In this paper, we summarize the structure, content, and functions of exosomes and the potential diagnostic and therapeutic applications of exosome-associated microRNAs in the treatment of metabolic disorders.

概要

代谢性疾病是指包括代谢综合征、肥胖和糖尿病 在内的一系列复杂疾病。其中脂毒性、慢性炎症 和氧化应激可以通过改变细胞功能,从而在代谢 紊乱的病理进程中发挥重要作用。近期研究发现 细胞可以分泌含有蛋白质、脂质、核酸的纳米级 微小囊泡,介导相邻和远处细胞间的信号传导和 物质转运。外泌体作为这类囊泡的一种,参与包 括肿瘤转移、动脉粥样硬化、慢性炎症和胰岛素 抵抗等多种病理过程。外泌体的研究大多集中于 其所含的蛋白质, 而近期关于外泌体相关 microRNA 的功能研究也日益受到关注。尤其是, 现已证明外泌体相关microRNA 参与了机体代谢 的诸多生理、病理进程,为代谢性疾病的诊断和 治疗提供了新的方向。本文总结了外泌体的结 构、内容物及产生的机制(图1 和图2);体液 和细胞培养液中外泌体所含microRNA 的种类、 靶器官及其功能(表2);外泌体相关microRNA 在代谢性疾病中的作用,以及在诊断和治疗方面 的潜能。

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References

  • Ahadi A, Brennan S, Kennedy PJ, et al., 2016. Long non-coding RNAs harboring miRNA seed regions are enriched in prostate cancer exosomes. Sci Rep, 6:24922. https://doi.org/10.1038/srep24922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alvarez-Erviti L, Seow Y, Yin H, et al., 2011. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol, 29(4):341–345. https://doi.org/10.1038/nbt.1807

    Article  CAS  PubMed  Google Scholar 

  • Aoki N, Yokoyama R, Asai N, et al., 2010. Adipocyte-derived microvesicles are associated with multiple angiogenic factors and induce angiogenesis in vivo and in vitro. Endocrinology, 151(6):2567–2576. https://doi.org/10.1210/en.2009-1023

    Article  CAS  PubMed  Google Scholar 

  • Asea A, Jean-Pierre C, Kaur P, et al., 2008. Heat shock proteincontaining exosomes in mid-trimester amniotic flunit. J Reprod Immunol, 79(1):12–17. https://doi.org/10.1016/j.jri.2008.06.001

    Article  CAS  PubMed  Google Scholar 

  • Au Yeung CL, Co NN, Tsuruga T, et al., 2016. Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1. Nat Commun, 7:11150. https://doi.org/10.1038/ncomms11150

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Belgardt BF, Ahmed K, Spranger M, et al., 2015. The microRNA-200 family regulates pancreatic ß cell survival in type 2 diabetes. Nat Med, 21(6):619–627. https://doi.org/10.1038/nm.3862

    Article  CAS  PubMed  Google Scholar 

  • Bobrie A, Colombo M, Raposo G, et al., 2011. Exosome secretion: molecular mechanisms and roles in immune responses. Traffic, 12(12):1659–1668. https://doi.org/10.1111/j.1600-0854.2011.01225.x

    Article  CAS  PubMed  Google Scholar 

  • Bosque A, Dietz L, Gallego-Lleyda A, et al., 2016. Comparative proteomics of exosomes secreted by tumoral jurkat T cells and normal human T cell blasts unravels a potential tumorigenic role for valosin-containing protein. Oncotarget, 7(20):29287–29305. https://doi.org/10.18632/oncotarget.8678

    Article  PubMed  PubMed Central  Google Scholar 

  • Bourderioux M, Nguyen-Khoa T, Chhuon C, et al., 2015. A new workflow for proteomic analysis of urinary exosomes and assessment in cystinuria patients. J Proteome Res, 14(1):567–577. https://doi.org/10.1021/pr501003q

    Article  CAS  PubMed  Google Scholar 

  • Cha DJ, Franklin JL, Dou Y, et al., 2015. KRAS-dependent sorting of miRNA to exosomes. Elife, 4:e07197. https://doi.org/10.7554/eLife.07197

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chaturvedi P, Kalani A, Medina I, et al., 2015. Cardiosome mediated regulation of MMP9 in diabetic heart: role of miR29b and miR455 in exercise. J Cell Mol Med, 19(9): 2153–2161.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen Y, Buyel JJ, Hanssen MJ, et al., 2016. Exosomal microRNA miR-92a concentration in serum reflects human brown fat activity. Nat Commun, 7:11420. https://doi.org/10.1038/ncomms11420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Conde-Vancells J, Rodriguez-Suarez E, Embade N, et al., 2008. Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes. J Proteome Res, 7(12):5157–5166. https://doi.org/10.1021/pr8004887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cortez MA, Bueso-Ramos C, Ferdin J, et al., 2011. MicroRNAs in body fluids—the mix of hormones and biomarkers. Nat Rev Clin Oncol, 8(8):467–477. https://doi.org/10.1038/nrclinonc.2011.76

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Csak T, Bala S, Lippai D, et al., 2015. MicroRNA-122 regulates hypoxia-inducible factor-1 and vimentin in hepatocytes and correlates with fibrosis in diet-induced steatohepatitis. Liver Int, 35(2):532–541. https://doi.org/10.1111/liv.12633

    Article  CAS  PubMed  Google Scholar 

  • de Jong OG, Verhaar MC, Chen Y, et al., 2012. Cellular stress conditions are reflected in the protein and RNA content of endothelial cell-derived exosomes. J Extracell Vesicles, 1(1):18396. https://doi.org/10.3402/jev.v1i0.18396

    Article  CAS  Google Scholar 

  • Delic D, Eisele C, Schmid R, et al., 2016. Urinary exosomal miRNA signature in type II diabetic nephropathy patients. PLoS ONE, 11(3):e0150154. https://doi.org/10.1371/journal.pone.0150154

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dirkx E, Gladka MM, Philippen LE, et al., 2013. Nfat and miR-25 cooperate to reactivate the transcription factor Hand2 in heart failure. Nat Cell Biol, 15(11):1282–1293. https://doi.org/10.1038/ncb2866

    Article  CAS  PubMed  Google Scholar 

  • Dragovic RA, Gardiner C, Brooks AS, et al., 2011. Sizing and phenotyping of cellular vesicles using nanoparticle tracking analysis. Nanomedicine, 7(6):780–788. https://doi.org/10.1016/j.nano.2011.04.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • El Andaloussi S, Mager I, Breakefield XO, et al., 2013. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov, 12(5):347–357. https://doi.org/10.1038/nrd3978

    Article  CAS  PubMed  Google Scholar 

  • Escola JM, Kleijmeer MJ, Stoorvogel W, et al., 1998. Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J Biol Chem, 273(32): 20121–20127. https://doi.org/10.1074/jbc.273.32.20121

    Article  CAS  PubMed  Google Scholar 

  • Escudier B, Dorval T, Chaput N, et al., 2005. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of the first phase I clinical trial. J Transl Med, 3(1):10. https://doi.org/10.1186/1479-5876-3-10

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fei F, Joo EJ, Tarighat SS, et al., 2015. B-cell precursor acute lymphoblastic leukemia and stromal cells communicate through galectin-3. Oncotarget, 6(13):11378–11394. https://doi.org/10.18632/oncotarget.3409

    Article  PubMed  PubMed Central  Google Scholar 

  • Felicetti F, de Feo A, Coscia C, et al., 2016. Exosomemediated transfer of miR-222 is sufficient to increase tumor malignancy in melanoma. J Transl Med, 14:56. https://doi.org/10.1186/s12967-016-0811-2

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fevrier B, Raposo G, 2004. Exosomes: endosomal-derived vesicles shipping extracellular messages. Curr Opin Cell Biol, 16(4):415–421. https://doi.org/10.1016/j.ceb.2004.06.003

    Article  CAS  PubMed  Google Scholar 

  • Gan X, Gould SJ, 2011. Identification of an inhibitory budding signal that blocks the release of HIV particles and exosome/microvesicle proteins. Mol Biol Cell, 22(6): 817–830. https://doi.org/10.1091/mbc.E10-07-0625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geiger A, Walker A, Nissen E, 2015. Human fibrocyte-derived exosomes accelerate wound healing in genetically diabetic mice. Biochem Biophys Res Commun, 467(2):303–309. https://doi.org/10.1016/j.bbrc.2015.09.166

    Article  CAS  PubMed  Google Scholar 

  • Harding C, Heuser J, Stahl P, 1984. Endocytosis and intracellular processing of transferrin and colloidal goldtransferrin in rat reticulocytes: demonstration of a pathway for receptor shedding. Eur J Cell Biol, 35(2):256–263.

    CAS  PubMed  Google Scholar 

  • Hawari FI, Rouhani FN, Cui X, et al., 2004. Release of full-length 55-kDa TNF receptor 1 in exosome-like vesicles: a mechanism for generation of soluble cytokine receptors. Proc Natl Acad Sci USA, 101(5):1297–1302. https://doi.org/10.1073/pnas.0307981100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hergenreider E, Heydt S, Treguer K, et al., 2012. Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol, 14(3):249–256. https://doi.org/10.1038/ncb2441

    Article  CAS  PubMed  Google Scholar 

  • Hirsova P, Ibrahim SH, Krishnan A, et al., 2016. Lipidinduced signaling causes release of inflammatory extracellular vesicles from hepatocytes. Gastroenterology, 150(4):956–967. https://doi.org/10.1053/j.gastro.2015.12.037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hood JL, San RS, Wickline SA, 2011. Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Res, 71(11):3792–3801. https://doi.org/10.1158/0008-5472.CAN-10-4455

    Article  CAS  PubMed  Google Scholar 

  • Horie T, Ono K, Horiguchi M, et al., 2010. MicroRNA-33 encoded by an intron of sterol regulatory element-binding protein 2 (SREBP2) regulates HDL in vivo. Proc Natl Acad Sci USA, 107(40):17321–17326. https://doi.org/10.1073/pnas.1008499107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hristov M, Erl W, Linder S, et al., 2004. Apoptotic bodies from endothelial cells enhance the number and initiate the differentiation of human endothelial progenitor cells in vitro. Blood, 104(9):2761–2766. https://doi.org/10.1182/blood-2003-10-3614

    Article  CAS  PubMed  Google Scholar 

  • Hsu C, Morohashi Y, Yoshimura S, et al., 2010. Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A–C. J Cell Biol, 189(2):223–232. https://doi.org/10.1083/jcb.200911018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang X, Yuan T, Tschannen M, et al., 2013. Characterization of human plasma-derived exosomal RNAs by deep sequencing. BMC Genomics, 14:319. https://doi.org/10.1186/1471-2164-14-319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johnstone RM, Adam M, Hammond JR, et al., 1987. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem, 262(19):9412–9420.

    CAS  PubMed  Google Scholar 

  • Jordan SD, Kruger M, Willmes DM, et al., 2011. Obesityinduced overexpression of miRNA-143 inhibits insulinstimulated AKT activation and impairs glucose metabolism. Nat Cell Biol, 13(4):434–446. https://doi.org/10.1038/ncb2211

    Article  CAS  PubMed  Google Scholar 

  • Kim JW, Wieckowski E, Taylor DD, et al., 2005. Fas ligandpositive membranous vesicles isolated from sera of patients with oral cancer induce apoptosis of activated T lymphocytes. Clin Cancer Res, 11(3):1010–1020.

    CAS  PubMed  Google Scholar 

  • Kloosterman WP, Lagendijk AK, Ketting RF, et al., 2007. Targeted inhibition of miRNA maturation with morpholinos reveals a role for miR-375 in pancreatic islet development. PLoS Biol, 5(8):e203. https://doi.org/10.1371/journal.pbio.0050203

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kornek M, Lynch M, Mehta SH, et al., 2012. Circulating microparticles as disease-specific biomarkers of severity of inflammation in patients with hepatitis C or nonalcoholic steatohepatitis. Gastroenterology, 143(2):448–458. https://doi.org/10.1053/j.gastro.2012.04.031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krutzfeldt J, Rajewsky N, Braich R, et al., 2005. Silencing of microRNAs in vivo with ‘antagomirs’. Nature, 438(7068): 685–689. https://doi.org/10.1038/nature04303

    Article  PubMed  CAS  Google Scholar 

  • Kuwabara Y, Ono K, Horie T, et al., 2011. Increased microRNA-1 and microRNA-133a levels in serum of patients with cardiovascular disease indicate myocardial damage. Circ Cardiovasc Genet, 4(4):446–454. https://doi.org/10.1161/CIRCGENETICS.110.958975

    Article  CAS  PubMed  Google Scholar 

  • Laulagnier K, Motta C, Hamdi S, et al., 2004. Mast cell-and dendritic cell-derived exosomes display a specific lipid composition and an unusual membrane organization. Biochem J, 380(1):161–171. https://doi.org/10.1042/bj20031594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee Y, El Andaloussi S, Wood MJ, 2012. Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy. Hum Mol Genet, 21(R1): R125–R134. https://doi.org/10.1093/hmg/dds317

    Article  CAS  PubMed  Google Scholar 

  • Lewis AP, Jopling CL, 2010. Regulation and biological function of the liver-specific miR-122. Biochem Soc Trans, 38(6):1553–1557. https://doi.org/10.1042/BST0381553

    Article  CAS  PubMed  Google Scholar 

  • Li M, Rai AJ, Decastro GJ, et al., 2015. An optimized procedure for exosome isolation and analysis using serum samples: application to cancer biomarker discovery. Methods, 87:26–30. https://doi.org/10.1016/j.ymeth.2015.03.009

    Article  PubMed  CAS  Google Scholar 

  • Liu D, Si B, Li C, et al., 2011. Prokaryotic expression and purification of HA1 and HA2 polypeptides for serological analysis of the 2009 pandemic H1N1 influenza virus. J Virol Methods, 172(1-2):16–21. https://doi.org/10.1016/j.jviromet.2010.12.007

    Article  CAS  PubMed  Google Scholar 

  • Lotvall J, Valadi H, 2007. Cell to cell signalling via exosomes through esRNA. Cell Adh Migr, 1(3):156–158. https://doi.org/10.4161/cam.1.3.5114

    Article  PubMed  PubMed Central  Google Scholar 

  • Mears R, Craven RA, Hanrahan S, et al., 2004. Proteomic analysis of melanoma-derived exosomes by twodimensional polyacrylamide gel electrophoresis and mass spectrometry. Proteomics, 4(12):4019–4031. https://doi.org/10.1002/pmic.200400876

    Article  CAS  PubMed  Google Scholar 

  • Milbank E, Martinez MC, Andriantsitohaina R, 2016. Extracellular vesicles: pharmacological modulators of the peripheral and central signals governing obesity. Pharmacol Ther, 157:65–83. https://doi.org/10.1016/j.pharmthera.2015.11.002

    Article  CAS  PubMed  Google Scholar 

  • Mitchell MD, Peiris HN, Kobayashi M, et al., 2015. Placental exosomes in normal and complicated pregnancy. Am J Obstet Gynecol, 213(4 Suppl):S173–S181. https://doi.org/10.1016/j.ajog.2015.07.001

    Article  CAS  PubMed  Google Scholar 

  • Mittelbrunn M, Gutierrez-Vazquez C, Villarroya-Beltri C, et al., 2011. Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat Commun, 2:282. https://doi.org/10.1038/ncomms1285

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Montecalvo A, Larregina AT, Shufesky WJ, et al., 2012. Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood, 119(3):756–766. https://doi.org/10.1182/blood-2011-02-338004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muller G, 2011. Control of lipid storage and cell size between adipocytes by vesicle-associated glycosylphosphatidylinositol-anchored proteins. Arch Physiol Biochem, 117(1): 23–43. https://doi.org/10.3109/13813455.2010.513393

    Article  PubMed  CAS  Google Scholar 

  • Muller L, Hong CS, Stolz DB, et al., 2014. Isolation of biologically-active exosomes from human plasma. J Immunol Methods, 411:55–65. https://doi.org/10.1016/j.jim.2014.06.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Najafi-Shoushtari SH, Kristo F, Li Y, et al., 2010. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science, 328(5985):1566–1569. https://doi.org/10.1126/science.1189123

    Article  CAS  PubMed  Google Scholar 

  • Nakano M, Nagaishi K, Konari N, et al., 2016. Bone marrowderived mesenchymal stem cells improve diabetesinduced cognitive impairment by exosome transfer into damaged neurons and astrocytes. Sci Rep, 6:24805. https://doi.org/10.1038/srep24805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Naslund TI, Gehrmann U, Qazi KR, et al., 2013. Dendritic cell-derived exosomes need to activate both T and B cells to induce antitumor immunity. J Immunol, 190(6):2712–2719. https://doi.org/10.4049/jimmunol.1203082

    Article  PubMed  CAS  Google Scholar 

  • Ogawa R, Tanaka C, Sato M, et al., 2010. Adipocyte-derived microvesicles contain RNA that is transported into macrophages and might be secreted into blood circulation. Biochem Biophys Res Commun, 398(4):723–729. https://doi.org/10.1016/j.bbrc.2010.07.008

    Article  CAS  PubMed  Google Scholar 

  • Ostrowski M, Carmo NB, Krumeich S, et al., 2010. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol, 12(1):19–30. https://doi.org/10.1038/ncb2000

    Article  CAS  PubMed  Google Scholar 

  • Pegtel DM, van de Garde MD, Middeldorp JM, 2011. Viral miRNAs exploiting the endosomal-exosomal pathway for intercellular cross-talk and immune evasion. Biochem Biophys Acta, 1809(11-12):715–721.

    CAS  PubMed  Google Scholar 

  • Phoonsawat W, Aoki-Yoshida A, Tsuruta T, et al., 2014. Adiponectin is partially associated with exosomes in mouse serum. Biochem Biophys Res Commun, 448(3): 261–266. https://doi.org/10.1016/j.bbrc.2014.04.114

    Article  CAS  PubMed  Google Scholar 

  • Pirola CJ, Fernandez Gianotti T, Castano GO, et al., 2015. Circulating microRNA signature in non-alcoholic fatty liver disease: from serum non-coding RNAs to liver histology and disease pathogenesis. Gut, 64(5):800–812. https://doi.org/10.1136/gutjnl-2014-306996

    Article  CAS  PubMed  Google Scholar 

  • Pisitkun T, Shen RF, Knepper MA, 2004. Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci USA, 101(36):13368–13373. https://doi.org/10.1073/pnas.0403453101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Povero D, Eguchi A, Li H, et al., 2014. Circulating extracellular vesicles with specific proteome and liver microRNAs are potential biomarkers for liver injury in experimental fatty liver disease. PLoS ONE, 9(12):e113651. https://doi.org/10.1371/journal.pone.0113651

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Poy MN, Eliasson L, Krutzfeldt J, et al., 2004. A pancreatic islet-specific microRNA regulates insulin secretion. Nature, 432(7014):226–230. https://doi.org/10.1038/nature03076

    Article  CAS  PubMed  Google Scholar 

  • Poy MN, Haußser J, Trajkovski M, et al., 2009. miR-375 maintains normal pancreatic a-and ß-cell mass. Proc Natl Acad Sci USA, 106(14):5813–5818. https://doi.org/10.1073/pnas.0810550106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pullen TJ, Da Silva Xavier G, Kelsey G, et al., 2011. miR-29a and miR-29b contribute to pancreatic ß-cell-specific silencing of monocarboxylate transporter 1 (Mct1). Mol Cell Biol, 31(15):3182–3194. https://doi.org/10.1128/MCB.01433-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rahman MJ, Regn D, Bashratyan R, et al., 2014. Exosomes released by islet-derived mesenchymal stem cells trigger autoimmune responses in nod mice. Diabetes, 63(3): 1008–1020. https://doi.org/10.2337/db13-0859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raiborg C, Stenmark H, 2009. The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature, 458(7237):445–452. https://doi.org/10.1038/nature07961

    Article  CAS  PubMed  Google Scholar 

  • Raposo G, Stoorvogel W, 2013. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol, 200(4): 373–383. https://doi.org/10.1083/jcb.201211138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raposo G, Nijman HW, Stoorvogel W, et al., 1996. B lymphocytes secrete antigen-presenting vesicles. J Exp Med, 183(3):1161–1172. https://doi.org/10.1084/jem.183.3.1161

    Article  CAS  PubMed  Google Scholar 

  • Rider MA, Hurwitz SN, Meckes DG, et al., 2016. ExtraPEG: a polyethylene glycol-based method for enrichment of extracellular vesicles. Sci Rep, 6:23978. https://doi.org/10.1038/srep23978

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Runz S, Keller S, Rupp C, et al., 2007. Malignant ascitesderived exosomes of ovarian carcinoma patients contain CD24 and EpCAM. Gynecol Oncol, 107(3):563–571. https://doi.org/10.1016/j.ygyno.2007.08.064

    Article  CAS  PubMed  Google Scholar 

  • Rupp AK, Rupp C, Keller S, et al., 2011. Loss of EpCAM expression in breast cancer derived serum exosomes: role of proteolytic cleavage. Gynecol Oncol, 122(2):437–446. https://doi.org/10.1016/j.ygyno.2011.04.035

    Article  CAS  PubMed  Google Scholar 

  • Salomon C, Scholz-Romero K, Sarker S, et al., 2016. Gestational diabetes mellitus is associated with changes in the concentration and bioactivity of placenta-derived exosomes in maternal circulation across gestation. Diabetes, 65(3):598–609. https://doi.org/10.2337/db15-0966

    Article  CAS  PubMed  Google Scholar 

  • Sohn W, Kim J, Kang SH, et al., 2015. Serum exosomal microRNAs as novel biomarkers for hepatocellular carcinoma. Exp Mol Med, 47:e184. https://doi.org/10.1038/emm.2015.68

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Street JM, Barran PE, Mackay CL, et al., 2012. Identification and proteomic profiling of exosomes in human cerebrospinal fluid. J Transl Med, 10:5. https://doi.org/10.1186/1479-5876-10-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stenmark H, 2009. Rab GTPases as coordinators of vesicle traffic. Nat Rev Mol Cell Biol, 10(8):513–525. https://doi.org/10.1038/nrm2728

    Article  CAS  PubMed  Google Scholar 

  • Subra C, Grand D, Laulagnier K, et al., 2010. Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins. J Lipid Res, 51(8):2105–2120. https://doi.org/10.1194/jlr.M003657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun L, Xie H, Mori MA, et al., 2011. Mir193b-365 is essential for brown fat differentiation. Nat Cell Biol, 13(8):958–965. https://doi.org/10.1038/ncb2286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun L, Wang X, Zhou Y, et al., 2016. Exosomes contribute to the transmission of anti-HIV activity from TLR3-activated brain microvascular endothelial cells to macrophages. Antiviral Res, 134:167–171. https://doi.org/10.1016/j.antiviral.2016.07.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tan SS, Yin Y, Lee T, et al., 2013. Therapeutic MSC exosomes are derived from lipid raft microdomains in the plasma membrane. J Extracell Vesicles, 2(1):22614. https://doi.org/10.3402/jev.v2i0.22614

    Article  CAS  Google Scholar 

  • Taylor DD, Gercel-Taylor C, 2008. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol, 110(1):13–21. https://doi.org/10.1016/j.ygyno.2008.04.033

    Article  CAS  PubMed  Google Scholar 

  • Thery C, Amigorena S, Raposo G, et al., 2006. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. In: Bonifacino JS, Harford JB, Lippincott-Schwartz J (Eds.), Current Protocols in Cell Biology. Wiley Online Library, p.3–22. https://doi.org/10.1002/0471143030.cb0322s30

    Google Scholar 

  • Tokarz A, Szuscik I, Kusnierz-Cabala B, et al., 2015. Extracellular vesicles participate in the transport of cytokines and angiogenic factors in diabetic patients with ocular complications. Folia Med Cracov, 55(4):35–48.

    PubMed  Google Scholar 

  • Trajkovski M, Hausser J, Soutschek J, et al., 2011. MicroRNAs 103 and 107 regulate insulin sensitivity. Nature, 474(7353):649–653. https://doi.org/10.1038/nature10112

    Article  CAS  PubMed  Google Scholar 

  • Trams EG, Lauter CJ, Salem N, et al., 1981. Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim Biophys Acta, 645(1):63–70. https://doi.org/10.1016/0005-2736(81)90512-5

    Article  CAS  PubMed  Google Scholar 

  • Valadi H, Ekstrom K, Bossios A, et al., 2007. Exosomemediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol, 9(6):654–659. https://doi.org/10.1038/ncb1596

    Article  CAS  PubMed  Google Scholar 

  • van Balkom BW, de Jong OG, Smits M, et al., 2013. Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells. Blood, 121(19):3997–4006. https://doi.org/10.1182/blood-2013-02-478925

    Article  PubMed  CAS  Google Scholar 

  • van Balkom BW, Eisele AS, Pegtel DM, et al., 2015. Quantitative and qualitative analysis of small RNAs in human endothelial cells and exosomes provides insights into localized RNA processing, degradation and sorting. J Extracell Vesicles, 4:26760. https://doi.org/10.3402/jev.v4.26760

    Article  PubMed  CAS  Google Scholar 

  • van Niel G, Porto-Carreiro I, Simoes S, et al., 2006. Exosomes: a common pathway for a specialized function. J Biochem, 140(1):13–21. https://doi.org/10.1093/jb/mvj128

    Article  PubMed  CAS  Google Scholar 

  • Vlassov AV, Magdaleno S, Setterquist R, et al., 2012. Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta, 1820(7):940–948. https://doi.org/10.1016/j.bbagen.2012.03.017

    Article  CAS  PubMed  Google Scholar 

  • Wan S, Zhou Z, Duan B, et al., 2008. Direct B cell stimulation by dendritic cells in a mouse model of lupus. Arthritis Rheum, 58(6):1741–1750. https://doi.org/10.1002/art.23515

    Article  CAS  PubMed  Google Scholar 

  • Wieckowski EU, Visus C, Szajnik M, et al., 2009. Tumor-derived microvesicles promote regulatory T cell expansion and induce apoptosis in tumor-reactive activated CD8+ T lymphocytes. J Immunol, 183(6):3720–3730. https://doi.org/10.4049/jimmunol.0900970

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilfred BR, Wang WX, Nelson PT, 2007. Energizing miRNA research: a review of the role of miRNAs in lipid metabolism, with a prediction that miR-103/107 regulates human metabolic pathways. Mol Genet Metab, 91(3):209–217. https://doi.org/10.1016/j.ymgme.2007.03.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yauch RL, Hemler ME, 2000. Specific interactions among transmembrane 4 superfamily (TM4SF) proteins and phosphoinositide 4-kinase. Biochem J, 351(3):629–637. https://doi.org/10.1042/bj3510629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zaborowski MP, Balaj L, Breakefield XO, et al., 2015. Extracellular vesicles: composition, biological relevance, and methods of study. Bioscience, 65(8):783–797. https://doi.org/10.1093/biosci/biv084

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang H, Guan M, Townsend KL, et al., 2015a. MicroRNA-455 regulates brown adipogenesis via a novel HIF1an-AMPK-PGC1a signaling network. EMBO Rep, 16(10): 1378–1393. https://doi.org/10.15252/embr.201540837

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang L, Zhang S, Yao J, et al., 2015b. Microenvironmentinduced PTEN loss by exosomal microRNA primes brain metastasis outgrowth. Nature, 527(7576):100–104. https://doi.org/10.1038/nature15376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Liu D, Chen X, et al., 2010. Secreted monocytic miR-150 enhances targeted endothelial cell migration. Mol Cell, 39(1):133–144. https://doi.org/10.1016/j.molcel.2010.06.010

    Article  CAS  PubMed  Google Scholar 

  • Zubiri I, Posada-Ayala M, Sanz-Maroto A, et al., 2014. Diabetic nephropathy induces changes in the proteome of human urinary exosomes as revealed by label-free comparative analysis. J Proteomics, 96:92–102. https://doi.org/10.1016/j.jprot.2013.10.037

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University / Shandong Key Laboratory of Endocrinology and Lipid Metabolism / Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, 250021, China

    Zhen-yu Yao, Shan-shan Shao, Shi-zhan Ma, Chong-bo Yang, Meng-zhu Li & Jia-jun Zhao

  2. Scientific Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China

    Wen-bin Chen & Ling Gao

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  1. Zhen-yu Yao
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  2. Wen-bin Chen
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  3. Shan-shan Shao
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  4. Shi-zhan Ma
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  5. Chong-bo Yang
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  6. Meng-zhu Li
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  7. Jia-jun Zhao
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  8. Ling Gao
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Correspondence to Ling Gao.

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Project supported by the National Natural Science Foundation of China (Nos. 81230018, 81430020, 81270869, 81670796, and 81500595)

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Yao, Zy., Chen, Wb., Shao, Ss. et al. Role of exosome-associated microRNA in diagnostic and therapeutic applications to metabolic disorders. J. Zhejiang Univ. Sci. B 19, 183–198 (2018). https://doi.org/10.1631/jzus.B1600490

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  • DOI: https://doi.org/10.1631/jzus.B1600490

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