Full Text:   <2799>

Summary:  <1830>

CLC number: R34

On-line Access: 2018-03-05

Received: 2016-10-28

Revision Accepted: 2017-05-30

Crosschecked: 2018-02-10

Cited: 0

Clicked: 5209

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Zhen-yu Yao

https://orcid.org/0000-0002-0616-8037

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2018 Vol.19 No.3 P.183-198

http://doi.org/10.1631/jzus.B1600490


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


Author(s):  Zhen-yu Yao, Wen-bin Chen, Shan-shan Shao, Shi-zhan Ma, Chong-bo Yang, Meng-zhu Li, Jia-jun Zhao, Ling Gao

Affiliation(s):  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; more

Corresponding email(s):   gaoling1@medmail.com.cn

Key Words:  Metabolic disorders, Exosome, Exosome-associated microRNA, Non-alcoholic fatty liver disease, Obesity, Diabetes mellitus


Zhen-yu Yao, Wen-bin Chen, Shan-shan Shao, Shi-zhan Ma, Chong-bo Yang, Meng-zhu Li, Jia-jun Zhao, Ling Gao. Role of exosome-associated microRNA in diagnostic and therapeutic applications to metabolic disorders[J]. Journal of Zhejiang University Science B, 2018, 19(3): 183-198.

@article{title="Role of exosome-associated microRNA in diagnostic and therapeutic applications to metabolic disorders",
author="Zhen-yu Yao, Wen-bin Chen, Shan-shan Shao, Shi-zhan Ma, Chong-bo Yang, Meng-zhu Li, Jia-jun Zhao, Ling Gao",
journal="Journal of Zhejiang University Science B",
volume="19",
number="3",
pages="183-198",
year="2018",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1600490"
}

%0 Journal Article
%T Role of exosome-associated microRNA in diagnostic and therapeutic applications to metabolic disorders
%A Zhen-yu Yao
%A Wen-bin Chen
%A Shan-shan Shao
%A Shi-zhan Ma
%A Chong-bo Yang
%A Meng-zhu Li
%A Jia-jun Zhao
%A Ling Gao
%J Journal of Zhejiang University SCIENCE B
%V 19
%N 3
%P 183-198
%@ 1673-1581
%D 2018
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1600490

TY - JOUR
T1 - Role of exosome-associated microRNA in diagnostic and therapeutic applications to metabolic disorders
A1 - Zhen-yu Yao
A1 - Wen-bin Chen
A1 - Shan-shan Shao
A1 - Shi-zhan Ma
A1 - Chong-bo Yang
A1 - Meng-zhu Li
A1 - Jia-jun Zhao
A1 - Ling Gao
J0 - Journal of Zhejiang University Science B
VL - 19
IS - 3
SP - 183
EP - 198
%@ 1673-1581
Y1 - 2018
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1600490


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. exosome-associated 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.

外泌体相关的microRNA在代谢性疾病诊断和治疗中的作用

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.
关键词:代谢性疾病;外泌体;外泌体相关microRNA;非酒精性脂肪肝;肥胖;糖尿病

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]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.

[2]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.

[3]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.

[4]Asea A, Jean-Pierre C, Kaur P, et al., 2008. Heat shock protein-containing exosomes in mid-trimester amniotic flunit. J Reprod Immunol, 79(1):12-17.

[5]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.

[6]Belgardt BF, Ahmed K, Spranger M, et al., 2015. The microRNA-200 family regulates pancreatic β cell survival in type 2 diabetes. Nat Med, 21(6):619-627.

[7]Bobrie A, Colombo M, Raposo G, et al., 2011. Exosome secretion: molecular mechanisms and roles in immune responses. Traffic, 12(12):1659-1668.

[8]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.

[9]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.

[10]Cha DJ, Franklin JL, Dou Y, et al., 2015. KRAS-dependent sorting of miRNA to exosomes. Elife, 4:e07197.

[11]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.

[12]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.

[13]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.

[14]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.

[15]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.

[16]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.

[17]Delic D, Eisele C, Schmid R, et al., 2016. Urinary exosomal miRNA signature in type II diabetic nephropathy patients. PLoS ONE, 11(3):e0150154.

[18]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.

[19]Dragovic RA, Gardiner C, Brooks AS, et al., 2011. Sizing and phenotyping of cellular vesicles using nanoparticle tracking analysis. Nanomedicine, 7(6):780-788.

[20]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.

[21]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.

[22]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.

[23]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.

[24]Felicetti F, de Feo A, Coscia C, et al., 2016. Exosome-mediated transfer of miR-222 is sufficient to increase tumor malignancy in melanoma. J Transl Med, 14:56.

[25]Fevrier B, Raposo G, 2004. Exosomes: endosomal-derived vesicles shipping extracellular messages. Curr Opin Cell Biol, 16(4):415-421.

[26]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.

[27]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.

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

[29]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.

[30]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.

[31]Hirsova P, Ibrahim SH, Krishnan A, et al., 2016. Lipid-induced signaling causes release of inflammatory extracellular vesicles from hepatocytes. Gastroenterology, 150(4):956-967.

[32]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.

[33]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.

[34]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.

[35]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.

[36]Huang X, Yuan T, Tschannen M, et al., 2013. Characterization of human plasma-derived exosomal RNAs by deep sequencing. BMC Genomics, 14:319.

[37]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.

[38]Jordan SD, Kruger M, Willmes DM, et al., 2011. Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism. Nat Cell Biol, 13(4):434-446.

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

[40]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.

[41]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.

[42]Krutzfeldt J, Rajewsky N, Braich R, et al., 2005. Silencing of microRNAs in vivo with ‘antagomirs’. Nature, 438(7068):685-689.

[43]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.

[44]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.

[45]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.

[46]Lewis AP, Jopling CL, 2010. Regulation and biological function of the liver-specific miR-122. Biochem Soc Trans, 38(6):1553-1557.

[47]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.

[48]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.

[49]Lotvall J, Valadi H, 2007. Cell to cell signalling via exosomes through esRNA. Cell Adh Migr, 1(3):156-158.

[50]Mears R, Craven RA, Hanrahan S, et al., 2004. Proteomic analysis of melanoma-derived exosomes by two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. Proteomics, 4(12):4019-4031.

[51]Milbank E, Martinez MC, Andriantsitohaina R, 2016. Extracellular vesicles: pharmacological modulators of the peripheral and central signals governing obesity. Pharmacol Ther, 157:65-83.

[52]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.

[53]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.

[54]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.

[55]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.

[56]Muller L, Hong CS, Stolz DB, et al., 2014. Isolation of biologically-active exosomes from human plasma. J Immunol Methods, 411:55-65.

[57]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.

[58]Nakano M, Nagaishi K, Konari N, et al., 2016. Bone marrow-derived mesenchymal stem cells improve diabetes-induced cognitive impairment by exosome transfer into damaged neurons and astrocytes. Sci Rep, 6:24805.

[59]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.

[60]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.

[61]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.

[62]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.

[63]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.

[64]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.

[65]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.

[66]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.

[67]Poy MN, Eliasson L, Krutzfeldt J, et al., 2004. A pancreatic islet-specific microRNA regulates insulin secretion. Nature, 432(7014):226-230.

[68]Poy MN, Hausser J, Trajkovski M, et al., 2009. miR-375 maintains normal pancreatic α- and β-cell mass. Proc Natl Acad Sci USA, 106(14):5813-5818.

[69]Pullen TJ, Da Silva Xavier G, Kelsey G, et al., 2011. miR-29a and miR-29b contribute to pancreatic β-cell-specific silencing of monocarboxylate transporter 1 (Mct1). Mol Cell Biol, 31(15):3182-3194.

[70]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.

[71]Raiborg C, Stenmark H, 2009. The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature, 458(7237):445-452.

[72]Raposo G, Stoorvogel W, 2013. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol, 200(4):373-383.

[73]Raposo G, Nijman HW, Stoorvogel W, et al., 1996. B lymphocytes secrete antigen-presenting vesicles. J Exp Med, 183(3):1161-1172.

[74]Rider MA, Hurwitz SN, Meckes DG, et al., 2016. ExtraPEG: a polyethylene glycol-based method for enrichment of extracellular vesicles. Sci Rep, 6:23978.

[75]Runz S, Keller S, Rupp C, et al., 2007. Malignant ascites-derived exosomes of ovarian carcinoma patients contain CD24 and EpCAM. Gynecol Oncol, 107(3):563-571.

[76]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.

[77]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.

[78]Sohn W, Kim J, Kang SH, et al., 2015. Serum exosomal microRNAs as novel biomarkers for hepatocellular carcinoma. Exp Mol Med, 47:e184.

[79]Street JM, Barran PE, Mackay CL, et al., 2012. Identification and proteomic profiling of exosomes in human cerebrospinal fluid. J Transl Med, 10:5.

[80]Stenmark H, 2009. Rab GTPases as coordinators of vesicle traffic. Nat Rev Mol Cell Biol, 10(8):513-525.

[81]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.

[82]Sun L, Xie H, Mori MA, et al., 2011. Mir193b-365 is essential for brown fat differentiation. Nat Cell Biol, 13(8):958-965.

[83]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.

[84]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.

[85]Taylor DD, Gercel-Taylor C, 2008. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol, 110(1):13-21.

[86]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.

[87]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.

[88]Trajkovski M, Hausser J, Soutschek J, et al., 2011. MicroRNAs 103 and 107 regulate insulin sensitivity. Nature, 474(7353):649-653.

[89]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.

[90]Valadi H, Ekstrom K, Bossios A, et al., 2007. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol, 9(6):654-659.

[91]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.

[92]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.

[93]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.

[94]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.

[95]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.

[96]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.

[97]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.

[98]Yauch RL, Hemler ME, 2000. Specific interactions among transmembrane 4 superfamily (TM4SF) proteins and phosphoinositide 4-kinase. Biochem J, 351(3):629-637.

[99]Zaborowski MP, Balaj L, Breakefield XO, et al., 2015. Extracellular vesicles: composition, biological relevance, and methods of study. Bioscience, 65(8):783-797.

[100]Zhang H, Guan M, Townsend KL, et al., 2015a. MicroRNA-455 regulates brown adipogenesis via a novel HIF1an-AMPK-PGC1α signaling network. EMBO Rep, 16(10):1378-1393.

[101]Zhang L, Zhang S, Yao J, et al., 2015b. Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth. Nature, 527(7576):100-104.

[102]Zhang Y, Liu D, Chen X, et al., 2010. Secreted monocytic miR-150 enhances targeted endothelial cell migration. Mol Cell, 39(1):133-144.

[103]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.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE