{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T13:48:51Z","timestamp":1781704131321,"version":"3.54.5"},"reference-count":71,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,8,28]],"date-time":"2019-08-28T00:00:00Z","timestamp":1566950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB\/TRR57 (projects P13 and Q3)"],"award-info":[{"award-number":["SFB\/TRR57 (projects P13 and Q3)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Interdisciplinary Centre for Clinical Research (IZKF)","award":["Project O3-1"],"award-info":[{"award-number":["Project O3-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Injury of the liver involves a wound healing partial reaction governed by hepatic stellate cells and portal fibroblasts. Individual members of the transforming growth factor-\u03b2 (TGF-\u03b2) superfamily including TGF-\u03b2 itself and bone morphogenetic proteins (BMP) exert diverse and partially opposing effects on pro-fibrogenic responses. Signaling by these ligands is mediated through binding to membrane integral receptors type I\/type II. Binding and the outcome of signaling is critically modulated by Endoglin (Eng), a type III co-receptor. In order to learn more about trafficking of Eng in liver cells, we investigated the membranal subdomain localization of full-length (FL)-Eng. We could show that FL-Eng is enriched in Caveolin-1-containing sucrose gradient fractions. Since lipid rafts contribute to the pool of exosomes, we could consequently demonstrate for the first time that exosomes isolated from cultured primary hepatic stellate cells and its derivatives contain Eng. Moreover, via adenoviral overexpression, we demonstrate that all liver cells have the capacity to direct Eng to exosomes, irrespectively whether they express endogenous Eng or not. Finally, we demonstrate that block of N-glycosylation does not interfere with dimerization of the receptor, but abrogates the secretion of soluble Eng (sol-Eng) and prevents exosomal targeting of FL-Eng.<\/jats:p>","DOI":"10.3390\/cells8090997","type":"journal-article","created":{"date-parts":[[2019,8,28]],"date-time":"2019-08-28T11:23:18Z","timestamp":1566991398000},"page":"997","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Endoglin Trafficking\/Exosomal Targeting in Liver Cells Depends on N-Glycosylation"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0821-441X","authenticated-orcid":false,"given":"Steffen","family":"Meurer","sequence":"first","affiliation":[{"name":"RWTH University Hospital Aachen, Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, D-52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almut Elisabeth","family":"Wimmer","sequence":"additional","affiliation":[{"name":"RWTH University Hospital Aachen, Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, D-52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eddy","family":"van de Leur","sequence":"additional","affiliation":[{"name":"RWTH University Hospital Aachen, Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, D-52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3888-0931","authenticated-orcid":false,"given":"Ralf","family":"Weiskirchen","sequence":"additional","affiliation":[{"name":"RWTH University Hospital Aachen, Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, D-52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1093\/abbs\/gmx126","article-title":"TGF-\u03b2 family co-receptor function and signaling","volume":"50","author":"Nickel","year":"2018","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1159\/000444556","article-title":"Liver fibrosis: From pathogenesis to novel therapies","volume":"34","author":"Weiskirchen","year":"2016","journal-title":"Dig. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4992","DOI":"10.2741\/3583","article-title":"BMP-7 as antagonist of organ fibrosis","volume":"14","author":"Weiskirchen","year":"2009","journal-title":"Front. Biosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/nature10152","article-title":"Latent TGF-\u03b2 structure and activation","volume":"474","author":"Shi","year":"2011","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1016\/j.ajpath.2016.07.011","article-title":"Fibrogenic signaling is suppressed in hepatic stellate cells through targeting of connective tissue growth factor (CCN2) by Cellular or Exosomal MicroRNA-199a-5p","volume":"186","author":"Chen","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/j.1582-4934.2006.tb00292.x","article-title":"Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-\u03b2 as major players and therapeutic targets","volume":"10","author":"Gressner","year":"2006","journal-title":"J. Cell. Mol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/ncb975","article-title":"Distinct endocytic pathways regulate TGF-\u03b2 receptor signalling and turnover","volume":"5","author":"Goodfellow","year":"2003","journal-title":"Nat. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.tcb.2017.04.005","article-title":"Transforming growth factor-\u03b2 receptors and Smads: Regulatory complexity and functional versatility","volume":"27","author":"Budi","year":"2017","journal-title":"Trends Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/s41580-018-0007-0","article-title":"Contextual determinants of TGF\u03b2 action in development, immunity and cancer","volume":"19","author":"David","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.1083\/jcb.109.6.3137","article-title":"Membrane-anchored and soluble forms of betaglycan, a polymorphic proteoglycan that binds transforming growth factor-\u03b2","volume":"109","author":"Andres","year":"1989","journal-title":"J. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8361","DOI":"10.1016\/S0021-9258(19)38892-1","article-title":"Primary structure of endoglin, an RGD-containing glycoprotein of human endothelial cells","volume":"265","author":"Gougos","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1093\/hmg\/9.5.745","article-title":"Expression analysis of endoglin missense and truncation mutations: Insights into protein structure and disease mechanisms","volume":"9","author":"Lux","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1042\/BJ20111923","article-title":"TGF-\u03b2 sensitivity is determined by N-linked glycosylation of the type II TGF-\u03b2 receptor","volume":"445","author":"Kim","year":"2012","journal-title":"Biochem. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"25716","DOI":"10.1074\/jbc.M116.748624","article-title":"Altering the proteoglycan state of transforming growth factor \u03b2 type III receptor (T\u03b2RIII)\/betaglycan modulates canonical Wnt\/\u03b2-catenin signaling","volume":"291","author":"Jenkins","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/0092-8674(91)90073-8","article-title":"Structure and expression of the membrane proteoglycan betaglycan, a component of the TGF-\u03b2 receptor system","volume":"67","author":"Cheifetz","year":"1991","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"14588","DOI":"10.1074\/jbc.M008866200","article-title":"Ligand binding and functional properties of betaglycan, a co-receptor of the transforming growth factor-beta superfamily. Specialized binding regions for transforming growth factor-beta and inhibin A","volume":"276","author":"Montiel","year":"2001","journal-title":"Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4018","DOI":"10.1038\/sj.emboj.7600386","article-title":"Endoglin promotes endothelial cell proliferation and TGF-beta\/ALK1 signal transduction","volume":"23","author":"Lebrin","year":"2004","journal-title":"EMBO J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1242\/jcs.023283","article-title":"L- and S-endoglin differentially modulate TGFbeta1 signaling mediated by ALK1 and ALK5 in L6E9 myoblasts","volume":"121","author":"Velasco","year":"2008","journal-title":"J. Cell Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.cellsig.2010.12.002","article-title":"Expression and functional analysis of endoglin in isolated liver cells and its involvement in fibrogenic Smad signalling","volume":"23","author":"Meurer","year":"2011","journal-title":"Cell. Signal."},{"key":"ref_20","first-page":"180","article-title":"Endoglin in liver fibrogenesis: Bridging basic science and clinical practice","volume":"5","author":"Meurer","year":"2014","journal-title":"World J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"21507","DOI":"10.1074\/jbc.M700176200","article-title":"The interaction of endoglin with beta-arrestin2 regulates transforming growth factor-beta-mediated ERK activation and migration in endothelial cells","volume":"282","author":"Lee","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"32527","DOI":"10.1074\/jbc.M803059200","article-title":"Endoglin promotes transforming growth factor beta-mediated Smad 1\/5\/8 signaling and inhibits endothelial cell migration through its association with GIPC","volume":"283","author":"Lee","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1093\/hmg\/10.13.1347","article-title":"Analysis of several endoglin mutants reveals no endogenous mature or secreted protein capable of interfering with normal endoglin function","volume":"10","author":"Paquet","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1093\/hmg\/ddu531","article-title":"Functional analysis of endoglin mutations from hereditary hemorrhagic telangiectasia type 1 patients reveals different mechanisms for endoglin loss of function","volume":"24","author":"Mallet","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"F\u00f6rg, T., Hafner, M., and Lux, A. (2014). Investigation of endoglin wild-type and missense mutant protein heterodimerisation using fluorescence microscopy based IF, BiFC and FRET analyses. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102998"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ali, B.R., Ben-Rebeh, I., John, A., Akawi, N.A., Milhem, R.M., Al-Shehhi, N.A., Al-Ameri, M.M., Al-Shamisi, S.A., and Al-Gazali, L. (2011). Endoplasmic reticulum quality control is involved in the mechanism of endoglin-mediated hereditary haemorrhagic telangiectasia. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026206"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"dmm034397","DOI":"10.1242\/dmm.034397","article-title":"Soluble endoglin regulates expression of angiogenesis-related proteins and induction of arteriovenous malformations in a mouse model of hereditary hemorrhagic telangiectasia","volume":"11","author":"Botella","year":"2018","journal-title":"Dis. Model. Mech."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4141","DOI":"10.1158\/0008-5472.CAN-09-4466","article-title":"Matrix metalloproteinase-14 (MT1-MMP)-mediated endoglin shedding inhibits tumor angiogenesis","volume":"70","author":"Hawinkels","year":"2010","journal-title":"Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/nm1429","article-title":"Soluble endoglin contributes to the pathogenesis of preeclampsia","volume":"12","author":"Venkatesha","year":"2006","journal-title":"Nat. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"30034","DOI":"10.1074\/jbc.M111.260133","article-title":"Soluble endoglin specifically binds bone morphogenetic proteins 9 and 10 via its orphan domain, inhibits blood vessel formation, and suppresses tumor growth","volume":"286","author":"Castonguay","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1161\/HYPERTENSIONAHA.118.11706","article-title":"Exosomes from women with preeclampsia induced vascular dysfunction by delivering sFlt (soluble Fms-like tyrosine kinase)-1 and sEng (soluble Endoglin) to endothelial cells","volume":"72","author":"Chang","year":"2018","journal-title":"Hypertension"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1002\/hep.28814","article-title":"Extracellular vesicles in liver pathobiology: Small particles with big impact","volume":"64","author":"Hirsova","year":"2016","journal-title":"Hepatology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/hep4.1290","article-title":"Combatting fibrosis: Exosome-based therapies in the regression of liver fibrosis","volume":"3","author":"Chen","year":"2018","journal-title":"Hepatol. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8530","DOI":"10.1096\/fj.201802675R","article-title":"Exosomes from actviated hepatic stellate cells contain GLUT1 and PKM2: A role for exosomes in metabolic switch of liver nonparenchymal cells","volume":"33","author":"Wan","year":"2019","journal-title":"FASEB J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3078","DOI":"10.1074\/jbc.M405411200","article-title":"Identification of endoglin in rat hepatic stellate cells: New insights into transforming growth factor \u03b2 receptor signaling","volume":"280","author":"Meurer","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1111\/liv.13595","article-title":"Endoglin in human liver disease and murine models of liver fibrosis\u2014A protective factor against liver fibrosis","volume":"38","author":"Alsamman","year":"2018","journal-title":"Liver Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1073\/pnas.95.5.2509","article-title":"A simplified system for generating recombinant adenoviruses","volume":"95","author":"He","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"P2_36","DOI":"10.1055\/s-2008-1037544","article-title":"Soluble endoglin modulated TGF-\u03b21 mediated signaling in isolated hepatocytes","volume":"46","author":"Meurer","year":"2008","journal-title":"Z. Gastroenterol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1099\/0022-1317-36-1-59","article-title":"Characteristics of a human cell line transformed by DNA from human adenovirus type 5","volume":"36","author":"Graham","year":"1977","journal-title":"J. Gen. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1136\/gut.2004.042127","article-title":"Human hepatic stellate cell lines, LX-1 and LX-2: New tools for analysis of hepatic fibrosis","volume":"54","author":"Xu","year":"2005","journal-title":"Gut"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1126\/science.6248960","article-title":"Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen","volume":"209","author":"Knowles","year":"1980","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Meurer, S.K., Alsamman, M., Sahin, H., Wasmuth, H.E., Kisseleva, T., Brenner, D.A., Trautwein, C., Weiskirchen, R., and Scholten, D. (2013). Overexpression of endoglin modulates TGF-\u03b21-signalling pathways in a novel immortalized mouse hepatic stellate cell line. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0056116"},{"key":"ref_43","first-page":"644","article-title":"Characterization of fat-storing cell lines derived from normal and CCl4-cirrhotic livers. Differences in the production of interleukin-6","volume":"65","author":"Greenwel","year":"1991","journal-title":"Lab. Investig."},{"key":"ref_44","first-page":"377","article-title":"Chinese hamster ovary cell mutants with multiple glycosylation defects for production of glycoproteins with minimal carbohydrate heterogeneity","volume":"9","author":"Stanley","year":"1989","journal-title":"Mol. Cell. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"426","DOI":"10.3389\/fphar.2018.00426","article-title":"N-glycosylation of Lipocalin 2 is not required for secretion or exosome targeting","volume":"9","author":"Meurer","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_46","first-page":"99","article-title":"Isolation and culture of hepatic stellate cells","volume":"117","author":"Weiskirchen","year":"2005","journal-title":"Methods Mol. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/978-1-4939-7113-8_11","article-title":"Isolation and culture of primary murine hepatic stellate cells","volume":"1627","author":"Weiskirchen","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"27031","DOI":"10.3402\/jev.v4.27031","article-title":"Optimized exosome isolation protocol for cell culture supernatant and human plasma","volume":"4","author":"Lobb","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Weiskirchen, R., Kneifel, J., Weiskirchen, S., van de Leur, E., Kunz, D., and Gressner, A.M. (2000). Comparative evaluation of gene delivery devices in primary cultures of rat hepatic stellate cells and rat myofibroblasts. BMC Cell Biol., 1.","DOI":"10.1186\/1471-2121-1-4"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s00018-017-2595-9","article-title":"Current knowledge on exosome biogenesis and release","volume":"75","author":"Hessvik","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.mam.2018.06.003","article-title":"Organ and tissue fibrosis: Molecular signals, cellular mechanisms and translational implications","volume":"65","author":"Weiskirchen","year":"2019","journal-title":"Mol. Asp. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"11444","DOI":"10.1074\/jbc.272.17.11444","article-title":"Biosynthesis of the type I and type II TGF-beta receptors. Implications for complex formation","volume":"272","author":"Wells","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1161\/01.RES.0000159936.38601.22","article-title":"A role for endoglin in coupling eNOS activity and regulating vascular tone revealed in hereditary hemorrhagic telangiectasia","volume":"96","author":"Toporsian","year":"2005","journal-title":"Circ. Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Ilha, M., Moraes, K.D.S., Rohden, F., Martins, L.A.M., Borojevic, R., Lenz, G., Barb\u00e9-Tuana, F., and Guma, F.C.R. (2019). Exogenous expression of caveolin-1 is sufficient for hepatic stellate cell activation. J. Cell. Biochem.","DOI":"10.1002\/jcb.29226"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Jabalee, J., Towle, R., and Garnis, C. (2018). The role of extracellular vesicles in cancer: Cargo, function, and therapeutic implications. Cells, 7.","DOI":"10.3390\/cells7080093"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Gould, S.J., and Raposo, G. (2013). As we wait: Coping with an imperfect nomenclature for extracellular vesicles. J. Extracell. Vesicles, 2.","DOI":"10.3402\/jev.v2i0.20389"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1146\/annurev-cellbio-101512-122326","article-title":"Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles","volume":"30","author":"Colombo","year":"2014","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Holman, N.S., Church, R.J., Nautiyal, M., Rose, K.A., Thacker, S.E., Otieno, M.A., Wolf, K.K., LeCluyse, E., Watkins, P.B., and Mosedale, M. (2019). Hepatocyte-derived exosomes promote liver immune tolerance: Possible implications for idiosyncratic drug-induced liver injury. Toxicol. Sci.","DOI":"10.1093\/toxsci\/kfz112"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Liu, R., Li, X., Zhu, W., Wang, Y., Zhao, D., Wang, X., Gurley, E.C., Liang, G., Chen, W., and Lai, G. (2019). Cholangiocyte-derived exosomal long noncoding RNA H19 promotes hepatic stellate cell activation and cholestatic liver fibrosis. Hepatology.","DOI":"10.1002\/hep.30662"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Sasaki, R., Kanda, T., Yokosuka, O., Kato, N., Matsuoka, S., and Moriyama, M. (2019). Exosomes and hepatocellular carcinoma: From bench to bedside. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061406"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1002\/hep.26768","article-title":"Epigenetic regulation of connective tissue growth factor by MicroRNA-214 delivery in exosomes from mouse or human hepatic stellate cells","volume":"59","author":"Chen","year":"2014","journal-title":"Hepatology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5346","DOI":"10.1158\/0008-5472.CAN-11-0241","article-title":"Microvesicles released from human renal cancer stem cells stimulate angiogenesis and formation of lung premetastatic niche","volume":"71","author":"Grange","year":"2011","journal-title":"Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s00281-010-0234-8","article-title":"Exosomes\/microvesicles: Mediators of cancer-associated immunosuppressive microenvironments","volume":"33","author":"Taylor","year":"2011","journal-title":"Semin. Immunopathol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"442","DOI":"10.3389\/fimmu.2014.00442","article-title":"Tetraspanins in extracellular vesicle formation and function","volume":"5","author":"Andreu","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.2217\/nnm-2018-0094","article-title":"Caveolin-1-containing extracellular vesicles transport adhesion proteins and promote malignancy in breast cancer cell lines","volume":"13","author":"Campos","year":"2018","journal-title":"Nanomedicine"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"12172","DOI":"10.1038\/s41598-017-12491-4","article-title":"A single sphingomyelin species promotes exosomal release of Endoglin into the maternal circulation in preeclampsia","volume":"7","author":"Ermini","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4624","DOI":"10.1021\/pr200434y","article-title":"Identification of a conserved glycan signature for microvesicles","volume":"10","author":"Batista","year":"2011","journal-title":"J. Proteome Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"26290","DOI":"10.1074\/jbc.M114.572560","article-title":"Unfolded protein response is required for the definitive endodermal specification of mouse embryonic stem cells via Smad2 and \u03b2-catenin signaling","volume":"289","author":"Xu","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.livres.2018.01.001","article-title":"Extracellular vesicles in non-alcoholic and alcoholic fatty liver diseases","volume":"2","author":"Eguchi","year":"2018","journal-title":"Liver Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1111\/hepr.12794","article-title":"Emerging role of exosomes in liver physiology and pathology","volume":"47","author":"Cai","year":"2017","journal-title":"Hepatol. Res."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Han, W., and Duan, Z. (2019). Roles of exosomes in liver metastases: Novel diagnosis and treatment choices. J. Cell. Physiol.","DOI":"10.1002\/jcp.28785"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/9\/997\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:14:46Z","timestamp":1760188486000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/9\/997"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,28]]},"references-count":71,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["cells8090997"],"URL":"https:\/\/doi.org\/10.3390\/cells8090997","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,28]]}}}