SVF-derived extracellular vesicles carry characteristic miRNAs in lipedema.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
29 04 2020
29 04 2020
Historique:
received:
23
09
2019
accepted:
08
04
2020
entrez:
1
5
2020
pubmed:
1
5
2020
medline:
26
11
2020
Statut:
epublish
Résumé
Lipedema is a chronic, progressive disease of adipose tissue with lack of consistent diagnostic criteria. The aim of this study was a thorough comparative characterization of extracellular microRNAs (miRNAs) from the stromal vascular fraction (SVF) of healthy and lipedema adipose tissue. For this, we analyzed 187 extracellular miRNAs in concentrated conditioned medium (cCM) and specifically in small extracellular vesicles (sEVs) enriched thereof by size exclusion chromatography. No significant difference in median particle size and concentration was observed between sEV fractions in healthy and lipedema. We found the majority of miRNAs located predominantly in cCM compared to sEV enriched fraction. Surprisingly, hierarchical clustering of the most variant miRNAs showed that only sEVmiRNA profiles - but not cCMmiRNAs - were impacted by lipedema. Seven sEVmiRNAs (miR-16-5p, miR-29a-3p, miR-24-3p, miR-454-p, miR-144-5p, miR-130a-3p, let-7c-5p) were differently regulated in lipedema and healthy individuals, whereas only one cCMmiRNA (miR-188-5p) was significantly downregulated in lipedema. Comparing SVF from healthy and lipedema patients, we identified sEVs as the lipedema relevant miRNA fraction. This study contributes to identify the potential role of SVF secreted miRNAs in lipedema.
Identifiants
pubmed: 32350368
doi: 10.1038/s41598-020-64215-w
pii: 10.1038/s41598-020-64215-w
pmc: PMC7190633
doi:
Substances chimiques
MicroRNAs
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7211Références
Torre, Y. S., Wadeea, R., Rosas, V.&Herbst, K. L.Lipedema: friend and foe. Hormone molecular biology and clinical investigation33, https://doi.org/10.1515/hmbci-2017-0076 (2018).
Wollina, U. Lipedema-An update. Dermatologic Ther. 32, e12805, https://doi.org/10.1111/dth.12805 (2019).
doi: 10.1111/dth.12805
Wold, L. E., Hines, E. A. Jr. & Allen, E. V. Lipedema of the legs; a syndrome characterized by fat legs and edema. Ann. Intern. Med. 34, 1243–1250, https://doi.org/10.7326/0003-4819-34-5-1243 (1951).
doi: 10.7326/0003-4819-34-5-1243
pubmed: 14830102
Schneider, M., Conway, E. M. & Carmeliet, P. Lymph makes you fat. Nat. Genet. 37, 1023–1024, https://doi.org/10.1038/ng1005-1023 (2005).
doi: 10.1038/ng1005-1023
pubmed: 16195715
Szolnoky, G., Nemes, A., Gavaller, H., Forster, T. & Kemeny, L. Lipedema is associated with increased aortic stiffness. Lymphology 45, 71–79 (2012).
pubmed: 23057152
Al-Ghadban, S. et al. Dilated Blood and Lymphatic Microvessels, Angiogenesis, Increased Macrophages, and Adipocyte Hypertrophy in Lipedema Thigh Skin and Fat Tissue. J. Obes. 2019, 8747461, https://doi.org/10.1155/2019/8747461 (2019).
doi: 10.1155/2019/8747461
pubmed: 30949365
pmcid: 6425411
Priglinger, E. et al. The adipose tissue-derived stromal vascular fraction cells from lipedema patients: Are they different? Cytotherapy 19, 849–860, https://doi.org/10.1016/j.jcyt.2017.03.073 (2017).
doi: 10.1016/j.jcyt.2017.03.073
pubmed: 28454682
Suga, H. et al. Adipose tissue remodeling in lipedema: adipocyte death and concurrent regeneration. J. Cutan. Pathol. 36, 1293–1298, https://doi.org/10.1111/j.1600-0560.2009.01256.x (2009).
doi: 10.1111/j.1600-0560.2009.01256.x
pubmed: 19281484
Scheja, L. & Heeren, J. The endocrine function of adipose tissues in health and cardiometabolic disease. Nat. reviews. Endocrinol. 15, 507–524, https://doi.org/10.1038/s41574-019-0230-6 (2019).
doi: 10.1038/s41574-019-0230-6
Funcke, J. B.&Scherer, P. E.Beyond adiponectin and leptin: adipose tissue-derived mediators of inter-organ communication. Journal of lipid research, https://doi.org/10.1194/jlr.R094060 (2019).
Thomou, T. et al. Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature 542, 450–455, https://doi.org/10.1038/nature21365 (2017).
doi: 10.1038/nature21365
pubmed: 28199304
pmcid: 5330251
Ying, W. et al. Adipose Tissue Macrophage-Derived Exosomal miRNAs Can Modulate In Vivo and In Vitro Insulin Sensitivity. Cell 171, 372–384e312, https://doi.org/10.1016/j.cell.2017.08.035 (2017).
doi: 10.1016/j.cell.2017.08.035
pubmed: 28942920
Karastergiou, K. & Mohamed-Ali, V. The autocrine and paracrine roles of adipokines. Mol. Cell. Endocrinol. 318, 69–78, https://doi.org/10.1016/j.mce.2009.11.011 (2010).
doi: 10.1016/j.mce.2009.11.011
pubmed: 19948207
Weilner, S. et al. Vesicular Galectin-3 levels decrease with donor age and contribute to the reduced osteo-inductive potential of human plasma derived extracellular vesicles. Aging 8, 16–33, https://doi.org/10.18632/aging.100865 (2016).
doi: 10.18632/aging.100865
pubmed: 26752347
pmcid: 4761711
Weilner, S. et al. Secreted microvesicular miR-31 inhibits osteogenic differentiation of mesenchymal stem cells. Aging Cell 15, 744–754, https://doi.org/10.1111/acel.12484 (2016).
doi: 10.1111/acel.12484
pubmed: 27146333
pmcid: 4933673
Romeijn, J. R. M., de Rooij, M. J. M., Janssen, L. & Martens, H. Exploration of Patient Characteristics and Quality of Life in Patients with Lipoedema Using a Survey. Dermatology Ther. 8, 303–311, https://doi.org/10.1007/s13555-018-0241-6 (2018).
doi: 10.1007/s13555-018-0241-6
Sandhofer, M. et al.Prevention of Progression of Lipedema With Liposuction Using Tumescent Local Anesthesia; Results of an International Consensus Conference. Dermatologic surgery: official publication for American Society forDermatologic Surgery [et al.], https://doi.org/10.1097/DSS.0000000000002019 (2019).
Bauer, A. T. et al.Adipose stem cells from lipedema and control adipose tissue respond differently to adipogenic stimulation in vitro. Plastic and reconstructive surgery, https://doi.org/10.1097/PRS.0000000000005918 (2019).
Mitchell, P. S. et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc. Natl Acad. Sci. U S Am. 105, 10513–10518, https://doi.org/10.1073/pnas.0804549105 (2008).
doi: 10.1073/pnas.0804549105
Terlecki-Zaniewicz, L. et al. Small extracellular vesicles and their miRNA cargo are anti-apoptotic members of the senescence-associated secretory phenotype. Aging 10, 1103–1132, https://doi.org/10.18632/aging.101452 (2018).
doi: 10.18632/aging.101452
pubmed: 29779019
pmcid: 5990398
Holman, N. S., Mosedale, M., Wolf, K. K., LeCluyse, E. L. & Watkins, P. B. Subtoxic Alterations in Hepatocyte-Derived Exosomes: An Early Step in Drug-Induced Liver Injury? Toxicological sciences: an. Off. J. Soc. Toxicol. 151, 365–375, https://doi.org/10.1093/toxsci/kfw047 (2016).
doi: 10.1093/toxsci/kfw047
Turchinovich, A., Weiz, L., Langheinz, A. & Burwinkel, B. Characterization of extracellular circulating microRNA. Nucleic acids Res. 39, 7223–7233, https://doi.org/10.1093/nar/gkr254 (2011).
doi: 10.1093/nar/gkr254
pubmed: 21609964
pmcid: 3167594
Arroyo, J. D. et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc. Natl Acad. Sci. U S Am. 108, 5003–5008, https://doi.org/10.1073/pnas.1019055108 (2011).
doi: 10.1073/pnas.1019055108
Holnthoner, W. et al. Endothelial Cell-derived Extracellular Vesicles Size-dependently Exert Procoagulant Activity Detected by Thromboelastometry. Sci. Rep. 7, 3707, https://doi.org/10.1038/s41598-017-03159-0 (2017).
doi: 10.1038/s41598-017-03159-0
pubmed: 28623360
pmcid: 5473891
Wiklander, O. P. B. et al. Systematic Methodological Evaluation of a Multiplex Bead-Based Flow Cytometry Assay for Detection of Extracellular Vesicle Surface Signatures. Front. immunology 9, 1326, https://doi.org/10.3389/fimmu.2018.01326 (2018).
doi: 10.3389/fimmu.2018.01326
Fan, Y. et al. miRNet - dissecting miRNA-target interactions and functional associations through network-based visual analysis. Nucleic acids Res. 44, W135–141, https://doi.org/10.1093/nar/gkw288 (2016).
doi: 10.1093/nar/gkw288
pubmed: 27105848
pmcid: 4987881
Jassal, B. et al. The reactome pathway knowledgebase. Nucleic acids Res. 48, D498–D503, https://doi.org/10.1093/nar/gkz1031 (2020).
doi: 10.1093/nar/gkz1031
pubmed: 31691815
Metsalu, T. & Vilo, J. ClustVis: a web tool for visualizing clustering of multivariate data using Principal Component Analysis and heatmap. Nucleic acids Res. 43, W566–570, https://doi.org/10.1093/nar/gkv468 (2015).
doi: 10.1093/nar/gkv468
pubmed: 25969447
pmcid: 4489295
Crescenzi, R. et al. Tissue Sodium Content is Elevated in the Skin and Subcutaneous Adipose Tissue in Women with Lipedema. Obesity 26, 310–317, https://doi.org/10.1002/oby.22090 (2018).
doi: 10.1002/oby.22090
pubmed: 29280322
Child, A. H. et al. Lipedema: an inherited condition. Am. J. Med. genetics. Part. A 152A, 970–976, https://doi.org/10.1002/ajmg.a.33313 (2010).
doi: 10.1002/ajmg.a.33313
Waxler, J. L. et al. Altered body composition, lipedema, and decreased bone density in individuals with Williams syndrome: A preliminary report. Eur. J. Med. Genet. 60, 250–256, https://doi.org/10.1016/j.ejmg.2017.02.007 (2017).
doi: 10.1016/j.ejmg.2017.02.007
pubmed: 28254647
pmcid: 5490490
Stremersch, S., De Smedt, S. C. & Raemdonck, K. Therapeutic and diagnostic applications of extracellular vesicles. J. controlled release: Off. J. Controlled Rel. Soc. 244, 167–183, https://doi.org/10.1016/j.jconrel.2016.07.054 (2016).
doi: 10.1016/j.jconrel.2016.07.054
Samanta, S. et al. Exosomes: new molecular targets of diseases. Acta Pharmacol. Sin. 39, 501–513, https://doi.org/10.1038/aps.2017.162 (2018).
doi: 10.1038/aps.2017.162
pubmed: 29219950
Li, M. et al. MicroRNAs: control and loss of control in human physiology and disease. World J. Surg. 33, 667–684, https://doi.org/10.1007/s00268-008-9836-x (2009).
doi: 10.1007/s00268-008-9836-x
pubmed: 19030926
pmcid: 2933043
Malloci, M. et al. Extracellular Vesicles: Mechanisms in Human Health and Disease. Antioxid. redox Signal. 30, 813–856, https://doi.org/10.1089/ars.2017.7265 (2019).
doi: 10.1089/ars.2017.7265
pubmed: 29634347
Liang, B. et al. Characterization and proteomic analysis of ovarian cancer-derived exosomes. J. Proteom. 80, 171–182, https://doi.org/10.1016/j.jprot.2012.12.029 (2013).
doi: 10.1016/j.jprot.2012.12.029
Park, Y. H. et al. Prostate-specific extracellular vesicles as a novel biomarker in human prostate cancer. Sci. Rep. 6, 30386, https://doi.org/10.1038/srep30386 (2016).
doi: 10.1038/srep30386
pubmed: 27503267
pmcid: 4977541
Rupp, A. K. et al. Loss of EpCAM expression in breast cancer derived serum exosomes: role of proteolytic cleavage. Gynecologic Oncol. 122, 437–446, https://doi.org/10.1016/j.ygyno.2011.04.035 (2011).
doi: 10.1016/j.ygyno.2011.04.035
Cheruvanky, A. et al. Rapid isolation of urinary exosomal biomarkers using a nanomembrane ultrafiltration concentrator. Am. J. Physiol. Ren. physiology 292, F1657–1661, https://doi.org/10.1152/ajprenal.00434.2006 (2007).
doi: 10.1152/ajprenal.00434.2006
du Cheyron, D. et al. Urinary measurement of Na+/H+ exchanger isoform 3 (NHE3) protein as new marker of tubule injury in critically ill patients with ARF. Am. J. kidney diseases: Off. J. Natl Kidney Found. 42, 497–506, https://doi.org/10.1016/s0272-6386(03)00744-3 (2003).
doi: 10.1016/s0272-6386(03)00744-3
Zhou, H. et al. Urinary marker for oxidative stress in kidneys in cisplatin-induced acute renal failure in rats. Nephrology, dialysis, transplantation: Off. Publ. Eur. Dialysis Transpl. Assoc. - Eur. Ren. Assoc. 21, 616–623, https://doi.org/10.1093/ndt/gfi314 (2006).
doi: 10.1093/ndt/gfi314
Exosome Diagnostics, I. Clinical Validation of a Urinary Exosome Gene Signature in Men Presenting for Suspicion ofProstate Cancer. NCT02702856 (2015).
University of Alabama at, B., National Institute of Neurological, D. & Stroke. LRRK2and Other Novel Exosome Proteins in Parkinson’s Disease. NCT01860118 (2016).
University HospitalInselspital, B.&Universityof, Z. New Biomarkers and Difficult-to-treatHypertension. NCT03034265 (2017).
Sohel, M. H. Extracellular/Circulating microRNAs: release mechanisms, functions and challenges. Achiev. Life Sci. 10, 175–186 (2016).
Li, C. J. et al. MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation. J. Clin. investigation 125, 1509–1522, https://doi.org/10.1172/JCI77716 (2015).
doi: 10.1172/JCI77716
Hou, H. et al. MicroRNA-188-5p regulates contribution of bone marrow-derived cells to choroidal neovascularization development by targeting MMP-2/13. Exp. eye Res. 175, 115–123, https://doi.org/10.1016/j.exer.2018.06.010 (2018).
doi: 10.1016/j.exer.2018.06.010
pubmed: 29908885
Szel, E., Kemeny, L., Groma, G. & Szolnoky, G. Pathophysiological dilemmas of lipedema. Med. hypotheses 83, 599–606, https://doi.org/10.1016/j.mehy.2014.08.011 (2014).
doi: 10.1016/j.mehy.2014.08.011
pubmed: 25200646
Pill, K. et al. Microvascular Networks From Endothelial Cells and Mesenchymal Stromal Cells From Adipose Tissue and Bone Marrow: A Comparison. Front. Bioeng. Biotechnol. 6, 156, https://doi.org/10.3389/fbioe.2018.00156 (2018).
doi: 10.3389/fbioe.2018.00156
pubmed: 30410879
pmcid: 6209673
Luo, J. & Xiao, Q. A novel approach for predicting microRNA-disease associations by unbalanced bi-random walk on heterogeneous network. J. Biomed. Inform. 66, 194–203, https://doi.org/10.1016/j.jbi.2017.01.008 (2017).
doi: 10.1016/j.jbi.2017.01.008
pubmed: 28104458
Dickman, C. T. et al. Selective extracellular vesicle exclusion of miR-142-3p by oral cancer cells promotes both internal and extracellular malignant phenotypes. Oncotarget 8, 15252–15266, https://doi.org/10.18632/oncotarget.14862 (2017).
doi: 10.18632/oncotarget.14862
pubmed: 28146434
pmcid: 5362484
Pallante, P., Battista, S., Pierantoni, G. M. & Fusco, A. Deregulation of microRNA expression in thyroid neoplasias. Nature reviews. Endocrinology 10, 88–101, https://doi.org/10.1038/nrendo.2013.223 (2014).
doi: 10.1038/nrendo.2013.223
pubmed: 24247220
Hossain, M. M., Sohel, M. M., Schellander, K. & Tesfaye, D. Characterization and importance of microRNAs in mammalian gonadal functions. Cell tissue Res. 349, 679–690, https://doi.org/10.1007/s00441-012-1469-6 (2012).
doi: 10.1007/s00441-012-1469-6
pubmed: 22842772
Derghal, A., Djelloul, M., Trouslard, J. & Mounien, L. An Emerging Role of micro-RNA in the Effect of the Endocrine Disruptors. Front. Neurosci. 10, 318, https://doi.org/10.3389/fnins.2016.00318 (2016).
doi: 10.3389/fnins.2016.00318
pubmed: 27445682
pmcid: 4928026
Karbiener, M. et al. MicroRNA-26 family is required for human adipogenesis and drives characteristics of brown adipocytes. Stem Cell 32, 1578–1590, https://doi.org/10.1002/stem.1603 (2014).
doi: 10.1002/stem.1603
Lee, E. K. et al. miR-130 suppresses adipogenesis by inhibiting peroxisome proliferator-activated receptor gamma expression. Mol. Cell. Biol. 31, 626–638, https://doi.org/10.1128/MCB.00894-10 (2011).
doi: 10.1128/MCB.00894-10
pubmed: 21135128
Qin, L. et al. A deep investigation into the adipogenesis mechanism: profile of microRNAs regulating adipogenesis by modulating the canonical Wnt/beta-catenin signaling pathway. BMC genomics 11, 320, https://doi.org/10.1186/1471-2164-11-320 (2010).
doi: 10.1186/1471-2164-11-320
pubmed: 20492721
pmcid: 2895628
Frost, R. J. & Olson, E. N. Control of glucose homeostasis and insulin sensitivity by the Let-7 family of microRNAs. Proc. Natl Acad. Sci. U S Am. 108, 21075–21080, https://doi.org/10.1073/pnas.1118922109 (2011).
doi: 10.1073/pnas.1118922109
Pinnick, K. E. et al. Distinct developmental profile of lower-body adipose tissue defines resistance against obesity-associated metabolic complications. Diabetes 63, 3785–3797, https://doi.org/10.2337/db14-0385 (2014).
doi: 10.2337/db14-0385
pubmed: 24947352
Hilton, C. et al. MicroRNA-196a links human body fat distribution to adipose tissue extracellular matrix composition. EBioMedicine 44, 467–475, https://doi.org/10.1016/j.ebiom.2019.05.047 (2019).
doi: 10.1016/j.ebiom.2019.05.047
pubmed: 31151930
pmcid: 6607082
Banerjee, S. et al. MicroRNA let-7c regulates macrophage polarization. J. immunology 190, 6542–6549, https://doi.org/10.4049/jimmunol.1202496 (2013).
doi: 10.4049/jimmunol.1202496
Lv, J. et al. MicroRNA let-7c-5p improves neurological outcomes in a murine model of traumatic brain injury by suppressing neuroinflammation and regulating microglial activation. Brain Res. 1685, 91–104, https://doi.org/10.1016/j.brainres.2018.01.032 (2018).
doi: 10.1016/j.brainres.2018.01.032
pubmed: 29408500
Essandoh, K., Li, Y., Huo, J. & Fan, G. C. MiRNA-Mediated Macrophage Polarization and its Potential Role in the Regulation of Inflammatory Response. Shock 46, 122–131, https://doi.org/10.1097/SHK.0000000000000604 (2016).
doi: 10.1097/SHK.0000000000000604
pubmed: 26954942
pmcid: 26954942
Ng, L. F.et al.WNT Signaling in Disease. Cells 8, https://doi.org/10.3390/cells8080826 (2019).
Hu, H. H. et al. New insights into TGF-beta/Smad signaling in tissue fibrosis. Chemico-biological Interact. 292, 76–83, https://doi.org/10.1016/j.cbi.2018.07.008 (2018).
doi: 10.1016/j.cbi.2018.07.008
Bogaerts, E., Heindryckx, F., Vandewynckel, Y. P., Van Grunsven, L. A. & Van Vlierberghe, H. The roles of transforming growth factor-beta, Wnt, Notch and hypoxia on liver progenitor cells in primary liver tumours (Review). Int. J. Oncol. 44, 1015–1022, https://doi.org/10.3892/ijo.2014.2286 (2014).
doi: 10.3892/ijo.2014.2286
pubmed: 24504124
pmcid: 3977811
Gordeeva, O. TGFbeta Family Signaling Pathways in Pluripotent and Teratocarcinoma Stem Cells’ Fate Decisions: Balancing Between Self-Renewal, Differentiation, and Cancer. Cells 8, https://doi.org/10.3390/cells8121500 (2019).
Siebel, C. & Lendahl, U. Notch Signaling in Development, Tissue Homeostasis, and Disease. Physiological Rev. 97, 1235–1294, https://doi.org/10.1152/physrev.00005.2017 (2017).
doi: 10.1152/physrev.00005.2017
Aspalter, I. M. et al. Alk1 and Alk5 inhibition by Nrp1 controls vascular sprouting downstream of Notch. Nat. Commun. 6, 7264, https://doi.org/10.1038/ncomms8264 (2015).
doi: 10.1038/ncomms8264
pubmed: 26081042
pmcid: 4557308
Mouillesseaux, K. P. et al. Notch regulates BMP responsiveness and lateral branching in vessel networks via SMAD6. Nat. Commun. 7, 13247, https://doi.org/10.1038/ncomms13247 (2016).
doi: 10.1038/ncomms13247
pubmed: 27834400
pmcid: 5114582
Siems, W., Grune, T., Voss, P. & Brenke, R. Anti-fibrosclerotic effects of shock wave therapy in lipedema and cellulite. BioFactors 24, 275–282 (2005).
doi: 10.1002/biof.5520240132
Witwer, K. W. et al. Updating the MISEV minimal requirements for extracellular vesicle studies: building bridges to reproducibility. J. Extracell. Vesicles 6, 1396823, https://doi.org/10.1080/20013078.2017.1396823 (2017).
doi: 10.1080/20013078.2017.1396823
pubmed: 29184626
pmcid: 5698937