{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T11:21:45Z","timestamp":1793013705759,"version":"4.5.0"},"reference-count":152,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2019,9,4]],"date-time":"2019-09-04T00:00:00Z","timestamp":1567555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Independence of young Researchers (SIR)","award":["RBSI14D5NX"],"award-info":[{"award-number":["RBSI14D5NX"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Systemic sclerosis (SSc) is a rare autoimmune disease, characterized by vasculopathy and fibrosis of the skin and internal organs. This disease is still considered incurable and is associated with a high risk of mortality, which is related to fibrotic events. An early diagnosis is useful for preventing complications, and targeted therapies reduce disease progression and ameliorate patients\u2019 quality of life. Nevertheless, there are no validated biomarkers for early diagnosis with predictive prognostic value. Exosomes are membrane vesicles, transporting proteins and nucleic acids that may be delivered to target cells, which influences cellular behavior. They play important roles in cell\u2013cell communication, both in physiological and pathological conditions, and may be useful as circulating biomarkers. Recent evidences suggest a role for these microvesicles in the three main aspects related to the pathogenesis of SSc (immunity, vascular damage, and fibrosis). Moreover, exosomes are of particular interest in the field of nano-delivery and are used as biological carriers. In this review, we report the latest information concerning SSc pathogenesis, clinical aspects of SSc, and current approaches to the treatment of SSc. Furthermore, we indicate a possible role of exosomes in SSc pathogenesis and suggest their potential use as diagnostic and prognostic biomarkers, as well as therapeutic tools.<\/jats:p>","DOI":"10.3390\/ijms20184337","type":"journal-article","created":{"date-parts":[[2019,9,5]],"date-time":"2019-09-05T03:22:36Z","timestamp":1567653756000},"page":"4337","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Exosomes in Systemic Sclerosis: Messengers Between Immune, Vascular and Fibrotic Components?"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9433-4903","authenticated-orcid":false,"given":"Marta","family":"Colletti","sequence":"first","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology, IRCCS, Ospedale Pediatrico Bambino Ges\u00f9, Viale San Paolo 15, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Galardi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology, IRCCS, Ospedale Pediatrico Bambino Ges\u00f9, Viale San Paolo 15, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3196-1336","authenticated-orcid":false,"given":"Maria","family":"De Santis","sequence":"additional","affiliation":[{"name":"Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center-IRCCS\u2014Via Alessandro Manzoni, 56, 20089 Rozzano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo Maria","family":"Guidelli","sequence":"additional","affiliation":[{"name":"Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center-IRCCS\u2014Via Alessandro Manzoni, 56, 20089 Rozzano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Di Giannatale","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology, IRCCS, Ospedale Pediatrico Bambino Ges\u00f9, Viale San Paolo 15, 00146 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Di Luigi","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Movement, Human and Health Sciences, Universit\u00e0 degli Studi di Roma \u201cForo Italico\u201d, Piazza Lauro de Bosis, 600135 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4296-5081","authenticated-orcid":false,"given":"Cristina","family":"Antinozzi","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Department of Movement, Human and Health Sciences, Universit\u00e0 degli Studi di Roma \u201cForo Italico\u201d, Piazza Lauro de Bosis, 600135 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1136\/ard.2009.114264","article-title":"Causes and risk factors for death in systemic sclerosis: A study from the EULAR Scleroderma Trials and Research (EUSTAR) database","volume":"69","author":"Tyndall","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.mayocp.2013.01.018","article-title":"My Approach to the Treatment of Scleroderma","volume":"88","author":"Shah","year":"2013","journal-title":"Mayo. Clin. Proc."},{"key":"ref_3","first-page":"177","article-title":"Gender differences in systemic sclerosis: Relationship to clinical features, serologic status and outcomes","volume":"1","author":"Peoples","year":"2016","journal-title":"J. Scleroderma. Relat. Disord."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Subcommittee for scleroderma criteria of the american rheumatism association diagnostic and therapeutic criteria Committee (1980). Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum., 23, 581\u2013590.","DOI":"10.1002\/art.1780230510"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.it.2005.09.004","article-title":"Scleroderma: From cell and molecular mechanisms to disease models","volume":"26","author":"Abraham","year":"2005","journal-title":"Trends. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1093\/rheumatology\/kel285","article-title":"Immunological basis of systemic sclerosis","volume":"45","author":"Zuber","year":"2006","journal-title":"Rheumatology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.2741\/1654","article-title":"Immunology of systemic sclerosis","volume":"1","author":"Artlett","year":"2005","journal-title":"Front. Biosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1172\/JCI31139","article-title":"Systemic sclerosis: A prototypic multisystem fibrotic disorder","volume":"117","author":"Varga","year":"2007","journal-title":"J. Clin. Invest."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Burbelo, P.D., Gordon, S.M., Waldman, M., Edison, J.D., Little, D.J., Stitt, R.S., Bailey, W.T., Hughes, J.B., and Olson, S.W. (2019). Autoantibodies are present before the clinical diagnosis of systemic sclerosis. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0214202"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1056\/NEJMra0806188","article-title":"Scleroderma","volume":"7","author":"Gabrielli","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s11926-007-0012-3","article-title":"Autoimmunity in systemic sclerosis: Current concepts","volume":"9","author":"Boin","year":"2007","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1002\/art.11179","article-title":"In vivo analysis of the apoptosis-inducing effect of anti-endothelial cell antibodies in systemic sclerosis by the chorioallantonic membrane assay","volume":"48","author":"Worda","year":"2003","journal-title":"Arthritis Rheum."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1002\/art.1780360113","article-title":"Cyclosporine in systemic sclerosis: Results of a forty-eight\u2013week open safety study in ten patients","volume":"36","author":"Clements","year":"1993","journal-title":"Arthritis Rheum."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Morton, S.J., and Powell, R.J. (2000). Cyclosporin and tacrolimus: Their use in a routine clinical setting for scleroderma. Rheumatology, 865\u2013869.","DOI":"10.1093\/rheumatology\/39.8.865"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Crescioli, C., Corinaldesi, C., Riccieri, V., Raparelli, V., Vasile, M., Del Galdo, F., Valesini, G., Lenzi, A., Basili, S., and Antinozzi, C. (2018). Association of circulating CXCL10 and CXCL11 with systemic sclerosis. Ann. Rheum. Dis., 1845\u20131846.","DOI":"10.1136\/annrheumdis-2018-213257"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Daoussis, D., Liossis, S.N., Yiannopoulos, G., and Andonopoulos, A.P. (2011). B-cell depletion therapy in systemic sclerosis: Experimental rationale and update on clinical evidence. Int. J. Rheumatol., 214013.","DOI":"10.1155\/2011\/214013"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1002\/art.20274","article-title":"Altered blood B lymphocyte homeostasis in systemic sclerosis: Expanded naive B cells and diminished but activated B cells","volume":"50","author":"Sato","year":"2004","journal-title":"Arthritis Rheum."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1002\/art.20315","article-title":"Is systemic sclerosis an antigen-driven T cell disease?","volume":"50","author":"Sakkas","year":"2004","journal-title":"Arthritis Rheum."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1093\/rheumatology\/kem313","article-title":"CXCL10 (alpha) and CCL2 (beta) chemokines in systemic sclerosis--a longitudinal study","volume":"47","author":"Antonelli","year":"2008","journal-title":"Rheumatology"},{"key":"ref_20","first-page":"433","article-title":"Proteome-wide analysis and CXCL4 as a biomarker in systemic sclerosis","volume":"30","author":"Affandi","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_21","first-page":"328","article-title":"Elevated serum levels of interleukin-4 (IL-4), IL-10, and IL-13 in patients with systemic sclerosis","volume":"24","author":"Hasegawa","year":"1997","journal-title":"J. Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1002\/1529-0131(200011)43:11<2455::AID-ANR12>3.0.CO;2-K","article-title":"Increased IL-17 production in patients with systemic sclerosis","volume":"43","author":"Kurasawa","year":"2000","journal-title":"Arthritis Rheum."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Pillai, S. (2019). T and B lymphocytes in fibrosis and systemic sclerosis. Curr. Opin. Rheumatol.","DOI":"10.1097\/BOR.0000000000000644"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1080\/00015550152572976","article-title":"Systemic sclerosis-related Raynaud\u2019s phenomenon: Effects of iloprost infusion therapy on serum cytokine, growth factor and soluble adhesion molecule levels","volume":"81","author":"Mittag","year":"2001","journal-title":"Acta Derm Venereol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.autrev.2010.09.008","article-title":"Two faces of the same coin: Raynaud phenomenon and digital ulcers in systemic sclerosis","volume":"10","author":"Galluccio","year":"2011","journal-title":"Autoimmun. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1016\/S0140-6736(00)05118-7","article-title":"Raynaud\u2019s phenomenon","volume":"23","author":"Block","year":"2001","journal-title":"Lancet"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e360","DOI":"10.1542\/peds.113.4.e360","article-title":"Raynaud\u2019s phenomenon of the nipple: A treatable cause of painful breastfeeding","volume":"113","author":"Anderson","year":"2004","journal-title":"Pediatrics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1002\/art.37988","article-title":"Evidence that systemic sclerosis is a vascular disease","volume":"65","author":"Kahaleh","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1056\/NEJMcp013013","article-title":"Clinical practice. Raynaud\u2019s phenomenon","volume":"347","author":"Wigley","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_30","first-page":"105","article-title":"Vascular involvement in systemic sclerosis (scleroderma)","volume":"4","author":"Pattanaik","year":"2011","journal-title":"J. Inflamm. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1002\/art.1780340807","article-title":"Endothelin, an endothelial-dependent vasoconstrictor in scleroderma. Enhanced production and profibrotic action","volume":"34","author":"Kahaleh","year":"1991","journal-title":"Arthritis Rheum."},{"key":"ref_32","first-page":"1566","article-title":"Significance of plasma endothelin-1 levels in patients with systemic sclerosis","volume":"19","author":"Yamane","year":"1992","journal-title":"J. Rheumatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1002\/1529-0131(199905)42:5<930::AID-ANR11>3.0.CO;2-1","article-title":"Activation of microvascular pericytes in autoimmune Raynaud\u2019s phenomenon and systemic sclerosis","volume":"42","author":"Rajkumar","year":"1999","journal-title":"Arthritis Rheum."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.tcm.2009.04.002","article-title":"Regulator of G protein signaling 5: A new player in vascular remodeling","volume":"19","author":"Manzur","year":"2009","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1111\/j.0303-6987.2004.00203.x","article-title":"Hyperplasia of dermal microvascular pericytes in scleroderma","volume":"31","author":"Helmbold","year":"2004","journal-title":"J. Cutan. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1042\/CS20040262","article-title":"Contribution of prostanoids to endothelium-dependent vasodilatation in the digital circulation of women with primary Raynaud\u2019s disease","volume":"109","author":"Easter","year":"2005","journal-title":"Clin. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/art.1780380102","article-title":"Raynaud\u2019s phenomenon and scleroderma: Dysregulated neuroendothelial control of vascular tone","volume":"38","author":"Kahaleh","year":"1995","journal-title":"Arthritis Rheum."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kahaleh, B., and Mulligan-Kehoe, M.J. (2011). Mechanisms of vascular disease. Scleroderma, 227\u2013246.","DOI":"10.1007\/978-1-4419-5774-0_19"},{"key":"ref_39","first-page":"297","article-title":"Impaired response to mechanical fluid shear stress (MFSS) by scleroderma microvascular endothelial cells from involved and uninvolved skin","volume":"40","author":"Tomita","year":"1997","journal-title":"Arthritis Rheum."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Giuggioli, D., Manfredi, A., Lumetti, F., Colaci, M., and Ferri, C. (2018). Scleroderma skin ulcers definition, classification and treatment strategies our experience and review of the literature. Autoimmunity Rev., 155\u2013164.","DOI":"10.1016\/j.autrev.2017.11.020"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1093\/rheumatology\/kel310","article-title":"Nailfold capillaroscopy is useful for the diagnosis and follow-up of autoimmune rheumatic diseases. A future tool for the analysis of microvascular heart involvement?","volume":"45","author":"Cutolo","year":"2006","journal-title":"Rheumatology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3902","DOI":"10.1002\/art.24038","article-title":"Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud\u2019s phenomenon to systemic sclerosis: A twenty-year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis","volume":"58","author":"Koenig","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_43","first-page":"155","article-title":"Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis","volume":"27","author":"Cutolo","year":"2000","journal-title":"J. Rheumatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1136\/annrheumdis-2011-200780","article-title":"Do worsening scleroderma capillaroscopic patterns predictfuture severe organ involvement? A pilot study","volume":"71","author":"Smith","year":"2012","journal-title":"Ann. Rheum. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1136\/ard.2007.087353","article-title":"Nailfold capillary density is associated with the presence and severity of pulmonary arterial hypertension in systemic sclerosis","volume":"68","author":"Hofstee","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"ref_46","first-page":"81","article-title":"Decreased nailfold capillary density in limited scleroderma with pulmonary hypertension","volume":"16","author":"Ong","year":"1998","journal-title":"Asian Pac. J. Allergy Immunol."},{"key":"ref_47","first-page":"145","article-title":"Pulmonary hypertension in systemic sclerosis: Different phenotypes","volume":"27","author":"Launay","year":"2017","journal-title":"Eur. Respir. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Cano-Jim\u00e9nez, E., Hern\u00e1ndez Gonz\u00e1lez, F., and Peloche, G.B. (2018). Comorbidities and Complications in Idiopathic Pulmonary Fibrosis. Med. Sci., 6.","DOI":"10.3390\/medsci6030071"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"993","DOI":"10.4330\/wjc.v6.i9.993","article-title":"Cardiac manifestations in systemic sclerosis","volume":"26","author":"Lambova","year":"2014","journal-title":"World J. Cardiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1007\/s12016-009-8191-5","article-title":"Scleroderma renal crisis: A rare but severe complication of systemic sclerosis","volume":"40","author":"Mouthon","year":"2011","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Koch, A.E., and Distler, O. (2007). Vasculopathy and disordered angiogenesis in selected rheumatic diseases: Rheumatoid arthritis and systemic sclerosis. Arthritis Res. Ther., 9.","DOI":"10.1186\/ar2187"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/S0046-8177(97)90032-0","article-title":"Pathogenesis and evolution of plexiform lesions in pulmonary hypertension associated with scleroderma and human immunodeficiency virus infection","volume":"28","author":"Cool","year":"1997","journal-title":"Hum. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1093\/rheumatology\/kew017","article-title":"Serum levels of vascular dysfunction markers reflect disease severity and stage in systemic sclerosis patients","volume":"55","author":"Cossu","year":"2016","journal-title":"Rheumatology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.jdermsci.2010.06.008","article-title":"The impact of Fli1 deficiency on the pathogenesis of systemic sclerosis","volume":"59","author":"Asano","year":"2010","journal-title":"J. Dermatol. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2854","DOI":"10.1002\/art.23791","article-title":"Decreased expression of caveolin 1 in patients with systemic sclerosis: Crucial role in the pathogenesis of tissue fibrosis","volume":"58","author":"Sotgia","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5797","DOI":"10.1038\/ncomms6797","article-title":"Simultaneous downregulation of KLF5 and Fli1 is a key feature underlying systemic sclerosis","volume":"5","author":"Noda","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.autrev.2010.09.015","article-title":"Fibrosis in systemic sclerosis: Emerging concepts and implications for targeted therapy","volume":"10","author":"Wei","year":"2011","journal-title":"Autoimmun Rev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1067-1927.2005.130102.x","article-title":"Tissue repair, contraction, and the myofibroblast","volume":"13","author":"Desmouliere","year":"2005","journal-title":"Wound Repair Regen."},{"key":"ref_59","first-page":"5","article-title":"The myofibroblast in wound healing and fibrosis: Answered and unanswered questions","volume":"26","author":"Gabbiani","year":"2016","journal-title":"F1000 Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1007\/s11926-014-0474-z","article-title":"Emerging roles of innate immune signaling and toll-like receptors in fibrosis and systemic sclerosis","volume":"17","author":"Bhattacharyya","year":"2015","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1002\/art.1780390811","article-title":"Heterogeneity of collagen synthesis in normal and systemic sclerosis skin fibroblasts. Increased proportion of high collagen-producing cells in systemic sclerosis fibroblasts","volume":"39","author":"Jelaska","year":"1996","journal-title":"Arthritis Rheum."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1186\/ar1790","article-title":"Shared expression of phenotypic markers in systemic sclerosis indicates a convergence of pericytes and fibroblasts to a myofibroblast lineage in fibrosis","volume":"7","author":"Rajkumar","year":"2005","journal-title":"Arthritis Res. Ther."},{"key":"ref_63","first-page":"185","article-title":"The human Thy-1 molecule","volume":"45","author":"Dalchau","year":"1989","journal-title":"Immunol. Ser."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1126\/science.6177036","article-title":"Neuronal cell Thy-1 glycoprotein: Homology with immunoglobulin","volume":"216","author":"Williams","year":"1982","journal-title":"Science"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1002\/eji.201041117","article-title":"Thy-1 (CD90) regulates the extravasation of leukocytes during inflammation","volume":"41","author":"Schubert","year":"2011","journal-title":"Eur. J. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1002\/acr.21799","article-title":"Soluble CD90 as a potential marker of pulmonary involvement in systemic sclerosis","volume":"65","author":"Kollert","year":"2013","journal-title":"Arthritis Care Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/nrrheum.2014.137","article-title":"Transforming growth factor \u03b2--at the centre of systemic sclerosis","volume":"10","author":"Lafyatis","year":"2014","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4803","DOI":"10.1242\/jcs.03270","article-title":"All in the CCN family: Essential matricellular signaling modulators emerge from the bunker","volume":"119","author":"Leask","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1093\/rheumatology\/ken401","article-title":"Monocyte chemoattractant proteins in the pathogenesis of systemic sclerosis","volume":"48","author":"Distler","year":"2009","journal-title":"Rheumatology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/1465-9921-6-96","article-title":"Functional, radiological and biological markers of alveolitis and infections of the lower respiratory tract in patients with systemic sclerosis","volume":"6","author":"Bosello","year":"2005","journal-title":"Respir. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1136\/ard.2008.095299","article-title":"EULAR recommendations for the treatment of systemic sclerosis: A report from the EULAR Scleroderma Trials and Research group (EUSTAR)","volume":"68","author":"Avouac","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s00281-015-0505-5","article-title":"Vasculopathy in scleroderma","volume":"37","author":"Asano","year":"2015","journal-title":"Semin. Immunopathol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1002\/1529-0131(200108)44:8<1841::AID-ART322>3.0.CO;2-8","article-title":"Calcium-channel blockers for Raynaud\u2019s phenomenon in systemic sclerosis","volume":"44","author":"Thompson","year":"2001","journal-title":"Arthritis Rheum."},{"key":"ref_74","first-page":"1918","article-title":"Thermographic and symptomatic effect of a single dose of sildenafil citrate on Raynaud\u2019s phenomenon in patients with systemic sclerosis: A potential treatment","volume":"33","author":"Kumar","year":"2006","journal-title":"J. Rheumatol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1136\/ard.2009.116475","article-title":"Effect of sildenafil on digital ulcers in systemic sclerosis: Analysis from a single centre pilot study","volume":"69","author":"Brueckner","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1517\/13543780802525100","article-title":"Phosphodiesterase-5 inhibitors for the treatment of Raynaud\u2019s: A novel indication","volume":"18","author":"Derk","year":"2009","journal-title":"Expert. Opin. Investig. Drugs."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/s11926-009-0078-1","article-title":"Diagnosis and management of pulmonary hypertension in systemic sclerosis","volume":"12","author":"Sweiss","year":"2010","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1177\/2040622317693218","article-title":"Steps forward in the treatment of pulmonary arterial hypertension: Latest developments and clinical opportunities","volume":"8","author":"Badlam","year":"2017","journal-title":"Ther. Adv. Chronic. Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"530","DOI":"10.3109\/s10165-009-0199-4","article-title":"Long-term beneficial effects of statins on vascular manifestations in patients with systemic sclerosis","volume":"19","author":"Kuwana","year":"2009","journal-title":"Mod. Rheumatol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Baqir, M., Makol, A., Osborn, T.G., Bartholmai, B.J., and Ryu, J.H. (2017). Mycophenolate mofetil for scleroderma-related interstitial lung disease: A real world experience. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0177107"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1007\/s10067-010-1498-z","article-title":"Mycophenolate mofetil in systemic sclerosis-associated interstitial lung disease","volume":"29","author":"Koutroumpas","year":"2010","journal-title":"Clin. Rheumatol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/s13075-016-1015-0","article-title":"Cyclophosphamide versus mycophenolate mofetil in scleroderma interstitial lung disease (SSc-ILD) as induction therapy: A single-centre, retrospective analysis","volume":"18","author":"Shenoy","year":"2016","journal-title":"Arthritis Res. Ther."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2630","DOI":"10.1016\/S0140-6736(16)00232-4","article-title":"Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (faSScinate): A phase 2, randomised, controlled trial","volume":"387","author":"Khanna","year":"2016","journal-title":"Lancet"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1007\/s00296-010-1697-6","article-title":"Corticosteroids and the risk of scleroderma renal crisis: A systematic review","volume":"32","author":"Trang","year":"2012","journal-title":"Rheumatol. Int."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1056\/NEJMoa1903076","article-title":"Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease","volume":"380","author":"Distler","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/S0140-6736(01)06250-X","article-title":"Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: A randomised placebo-controlled study","volume":"358","author":"Channick","year":"2001","journal-title":"Lancet"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1056\/NEJMoa012212","article-title":"Bosentan therapy for pulmonary arterial hypertension","volume":"346","author":"Rubin","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1164\/rccm.200307-957OC","article-title":"for STRIDE-1 Study Group. Sitaxsentan therapy for pulmonary arterial hypertension","volume":"169","author":"Barst","year":"2004","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1016\/j.jacc.2006.01.057","article-title":"Treatment of pulmonary arterial hypertension with the selective endothelin-A receptor antagonist sitaxsentan","volume":"47","author":"Barst","year":"2006","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"S80","DOI":"10.1097\/01.fjc.0000166207.74178.d0","article-title":"STRIDE-1 study group. STRIDE 1: Effects of the selective ETA receptor antagonist, sitaxsentan sodium, in a patient population with pulmonary arterial hypertension that meets traditional inclusion criteria of previous pulmonary arterial hypertension trials","volume":"44","author":"Langleben","year":"2004","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1056\/NEJMoa050010","article-title":"Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group. Sildenafil citrate therapy for pulmonary arterial hypertension","volume":"353","author":"Ghofrani","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1183\/09059180.00006111","article-title":"Risk factors associated with pulmonary arterial hypertension in patients with systemic sclerosis and implications for screening","volume":"20","author":"Denton","year":"2011","journal-title":"Eur. Respir. Rev."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"127","DOI":"10.3109\/03009742.2010.508751","article-title":"Survival in patients with pulmonary arterial hypertension associated with systemic sclerosis from a swedish single centre: Prognosis still poor and prediction difficult","volume":"40","author":"Hesselstrand","year":"2011","journal-title":"Scand. J. Rheumatol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1002\/art.30423","article-title":"Systemic sclerosis-related pulmonary hypertension associated with interstitial lung disease: Impact of pulmonary arterial hypertension therapies","volume":"63","author":"Girgis","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e000533","DOI":"10.1136\/rmdopen-2017-000533","article-title":"Haematopoietic stem cell transplantation in systemic sclerosis","volume":"4","author":"Walker","year":"2018","journal-title":"RMD Open"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.3389\/fimmu.2018.02013","article-title":"Mesenchymal Stromal Cells Based Therapy in Systemic Sclerosis: Rational and Challenges","volume":"13","author":"Peltzer","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.3389\/fimmu.2018.02938","article-title":"Mesenchymal Stem Cells in Systemic Sclerosis: Allogenic or Autologous Approaches for Therapeutic Use?","volume":"14","author":"Rozier","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1186\/s13075-015-0819-7","article-title":"Update on mesenchymal stem cell-based therapy in lupus and scleroderma","volume":"3","author":"Cras","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4213","DOI":"10.1242\/dev.124.21.4213","article-title":"Differentiation of engrafted multipotent neural progenitors towards replacement of missing granule neurons in meander tail cerebellum may help determine the locus of mutant gene action","volume":"124","author":"Rosario","year":"1997","journal-title":"Development"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"695","DOI":"10.3727\/096368908786092702","article-title":"Myocardial repair achieved by the intramyocardial implantation of adult cardiomyocytes in combination with bone marrow cells","volume":"17","author":"Li","year":"2008","journal-title":"Cell Transplant."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s00018-014-1764-3","article-title":"Formation and role of exosomes in cancer","volume":"72","author":"Brinton","year":"2015","journal-title":"Cell Mol. Life Sci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/0009-8981(77)90054-7","article-title":"Spontaneous shedding of plasma membrane fragments by human cells in vivo and in vitro","volume":"81","author":"Wieme","year":"1977","journal-title":"Clin. Chim. Acta."},{"key":"ref_103","first-page":"5553","article-title":"Analysis of ESCRT functions in exosome biogenesis, composition and secretion hightights the heterogeneity of extracellular vesicles","volume":"126","author":"Colombo","year":"2013","journal-title":"J. Cell. Sci."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Wendler, F., Bota-Rabassedas, N., and Franch-Marro, X. (2013). Cancer becomes wasteful: Emerging roles of exosomes (dagger) in cell-fate determination. J. Extracell. Vesicles, 2.","DOI":"10.3402\/jev.v2i0.22390"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/nm0598-594","article-title":"Eradication of established murine tumors using a novel cell-free vaccine: Dendritic cell-derived exosomes","volume":"4","author":"Zitvogel","year":"1998","journal-title":"Nat. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/0092-8674(83)90040-5","article-title":"Fate of transferrin receptor during maturation of sheep reticolocytes in vitro: Selective externalization of the receptor","volume":"33","author":"Pan","year":"1983","journal-title":"Cell"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nrm1959","article-title":"Mechanism of pathogen entry through the endosomal compartments","volume":"7","author":"Gruenberg","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.4049\/jimmunol.165.3.1259","article-title":"Follicular dendritic cells carry MHC class II-expressing microvesicles at their surface","volume":"165","author":"Denzer","year":"2000","journal-title":"J. Immunol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/S0092-8674(01)00484-6","article-title":"Argosomes: A potential vehicle for the spread of morphogens through epithelia","volume":"106","author":"Greco","year":"2001","journal-title":"Cell"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/77498","article-title":"Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: A mechanism for cellular human immunodeficiency virus infection","volume":"6","author":"Mack","year":"2000","journal-title":"Nat. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/nature08910","article-title":"The endocytic matrix","volume":"463","author":"Scita","year":"2010","journal-title":"Nature"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1084\/jem.183.3.1161","article-title":"B lymphocytes secrete antigen-presenting vesicles","volume":"1","author":"Raposo","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Van der Vlist, E.J., Arkesteijn, G.J., van de Lest, C.H., Stoorvogel, W., Nolte-\u2019t Hoen, E.N., and Wauben, M.H. (2012). CD4(+) T cell activation promotes the differential release of distinct populations of nanosized vesicles. J. Extracell. Vesicles, 1.","DOI":"10.3402\/jev.v1i0.18364"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1182\/blood-2004-03-0824","article-title":"Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells","volume":"15","author":"Morelli","year":"2004","journal-title":"Blood"},{"key":"ref_115","first-page":"2126","article-title":"Exosomes as potent cell-free peptide-based vaccine. I. Dendritic cell-derived exosomes transfer functional MHC class I\/peptide complexes to dendritic cells","volume":"15","author":"Chaput","year":"2004","journal-title":"J. Immunol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"3081","DOI":"10.4049\/jimmunol.180.5.3081","article-title":"Exosomes as a short-range mechanism to spread alloantigen between dendritic cells during T cell allorecognition","volume":"1","author":"Montecalvo","year":"2008","journal-title":"J. Immunol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"7385","DOI":"10.4049\/jimmunol.176.12.7385","article-title":"A membrane form of TNF-alpha presented by exosomes delays T cell activation-induced cell death","volume":"15","author":"Zhang","year":"2006","journal-title":"J. Immunol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"3809","DOI":"10.1002\/art.22276","article-title":"Association of citrullinated proteins with synovial exosomes","volume":"54","author":"Skriner","year":"2006","journal-title":"Arthritis Rheum."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1038\/labinvest.2010.152","article-title":"Role of extracellular membrane vesicles in the pathogenesis of various diseases, including cancer, renal diseases, atherosclerosis, and arthritis","volume":"90","author":"Anderson","year":"2010","journal-title":"Lab. Invest."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1186\/s13075-016-1159-y","article-title":"Circulating exosomes from patients with systemic lupus erythematosus induce an proinflammatory immune response","volume":"16","author":"Lee","year":"2016","journal-title":"Arthritis Res. Ther."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1172\/JCI118851","article-title":"Endothelial cell apoptosis is a primary pathogenetic event underlying skin lesions in avian and human scleroderma","volume":"98","author":"Sgonc","year":"1996","journal-title":"J. Clin. Invest."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1160\/TH07-11-0691","article-title":"Monocyte-derived microparticles and exosomes induce procoagulant and apoptotic effects on endothelial cells","volume":"100","author":"Aharon","year":"2008","journal-title":"Thromb. Haemost."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/cmi.2010.59","article-title":"CD4(+) T cell-released exosomes inhibit CD8(+) cytotoxic T-lymphocyte responses and antitumor immunity","volume":"8","author":"Zhang","year":"2011","journal-title":"Cell Mol. Immunol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.immuni.2014.05.019","article-title":"MicroRNA-containing T-regulatory-cell-derived exosomes suppress pathogenic T helper 1 cells","volume":"17","author":"Okoye","year":"2014","journal-title":"Immunity"},{"key":"ref_125","unstructured":"Di Paolo, V., Colletti, M., Ferruzzi, V., Russo, I., Galardi, A., Alessi, I., Milano, G.M., and Di Giannatale, A. (2018). Circulating Biomarkers for Tumor Angiogenesis: Where Are We?. Curr. Med. Chem."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"4306","DOI":"10.1172\/JCI60658","article-title":"Molecular pathogenesis of pulmonary arterial hypertension","volume":"122","author":"Rabinovitch","year":"2012","journal-title":"J. Clin. Invest."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1161\/CIRCRESAHA.115.306806","article-title":"MicroRNA-143 Activation Regulates Smooth Muscle and Endothelial Cell Crosstalk in Pulmonary Arterial Hypertension","volume":"23","author":"Deng","year":"2015","journal-title":"Circ. Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1161\/CIRCULATIONAHA.112.114173","article-title":"Exosomes mediate the cytoprotective action of mesenchymal stromal cells on hypoxia-induced pulmonary hypertension","volume":"27","author":"Lee","year":"2012","journal-title":"Circulation"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1056\/NEJMra1300575","article-title":"Fibrosis--a common pathway to organ injury and failure","volume":"19","author":"Rockey","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jcmgh.2014.11.005","article-title":"Death Receptor-Mediated Cell Death and Proinflammatory Signaling in Nonalcoholic Steatohepatitis","volume":"1","author":"Hirsova","year":"2015","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1152\/ajprenal.00429.2016","article-title":"Extracellular vesicles in diagnosis and therapy of kidney diseases","volume":"1","author":"Zhang","year":"2016","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/978-981-10-4397-0_3","article-title":"Functional Role of Cardiovascular Exosomes in Myocardial Injury and Atherosclerosis","volume":"998","author":"Vanhaverbeke","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.chest.2017.06.026","article-title":"Extracellular Vesicles in Lung Disease","volume":"153","author":"Kubo","year":"2018","journal-title":"Chest"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1089\/scd.2012.0395","article-title":"Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis","volume":"15","author":"Li","year":"2013","journal-title":"Stem Cells Dev."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s12967-015-0417-0","article-title":"Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis","volume":"1","author":"Zhang","year":"2015","journal-title":"J. Transl. Med."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"32993","DOI":"10.1038\/srep32993","article-title":"Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts","volume":"2","author":"Hu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.5966\/sctm.2015-0367","article-title":"Umbilical Cord-Derived Mesenchymal Stem Cell-Derived Exosomal MicroRNAs Suppress Myofibroblast Differentiation by Inhibiting the Transforming Growth Factor-\u03b2\/SMAD2 Pathway During Wound Healing","volume":"5","author":"Fang","year":"2016","journal-title":"Stem Cells Transl. Med."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.jdermsci.2016.06.013","article-title":"Altered expression of CD63 and exosomes in scleroderma dermal fibroblasts","volume":"84","author":"Nakamura","year":"2016","journal-title":"J. Dermatol. Sci."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1002\/art.23735","article-title":"The relationship between plasma microparticles and disease manifestations in patients with systemic sclerosis","volume":"58","author":"Guiducci","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_140","first-page":"21","article-title":"Exosomes isolated from serum of systemic sclerosis patients display alterations in their content of profibrotic and antifibrotic microRNA and induce a profibrotic phenotype in cultured normal dermal fibroblasts","volume":"35","author":"Wermuth","year":"2017","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_141","first-page":"98","article-title":"Expression of Let-7 family microRNAs in skin correlates negatively with severity of pulmonary hypertension in patients with systemic scleroderma","volume":"18","author":"Izumiya","year":"2015","journal-title":"Int. J. Cardiol. Heart Vasc."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"3905","DOI":"10.4049\/jimmunol.1200822","article-title":"The downregulation of microRNA let-7a contributes to the excessive expression of type I collagen in systemic and localized scleroderma","volume":"15","author":"Makino","year":"2013","journal-title":"J. Immunol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1002\/art.27443","article-title":"MicroRNA-29, a key regulator of collagen expression in systemic sclerosis","volume":"62","author":"Maurer","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Ciechomska, M., O\u2019Reilly, S., Suwara, M., Bogunia-Kubik, K., and van Laar, J.M. (2014). MiR-29a reduces TIMP-1 production by dermal fibroblasts via targeting TGF-\u03b2 activated kinase 1 binding protein 1, implications for systemic sclerosis. PLoS ONE, 30.","DOI":"10.1371\/journal.pone.0115596"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"369","DOI":"10.3109\/08916934.2015.1030616","article-title":"MicroRNA-29a induces apoptosis via increasing the Bax:Bcl-2 ratio in dermal fibroblasts of patients with systemic sclerosis","volume":"48","author":"Farazmand","year":"2015","journal-title":"Autoimmunity"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.imlet.2018.10.002","article-title":"Impact of alterations in X-linked IRAK1gene and miR-146a on susceptibility and clinical manifestations in patients with systemic sclerosis","volume":"204","author":"Vreca","year":"2018","journal-title":"Immunol. Lett."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1365-2230.2012.04453.x","article-title":"The miR-146a rs2910164 C\/G polymorphism is associated with telangiectasia in systemic sclerosis","volume":"38","author":"Sakoguchi","year":"2013","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/cr.2017.11","article-title":"Mesenchymal stem cell transplantation in tight-skin mice identifies miR-151-5p as a therapeutic target for systemic sclerosis","volume":"27","author":"Chen","year":"2017","journal-title":"Cell Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1038\/mt.2016.90","article-title":"Mesenchymal Stem Cells Deliver Exogenous MicroRNA-let7c via Exosomes to Attenuate Renal Fibrosis","volume":"24","author":"Wang","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1111\/jcmm.13170","article-title":"Exosomes derived from miR-181-5p-modified adipose-derived mesenchymal stem cells prevent liver fibrosis via autophagy activation","volume":"21","author":"Qu","year":"2017","journal-title":"J. Cell Mol. Med."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1042\/BJ20150821","article-title":"miR-1343 attenuates pathways of fibrosis by targeting the TGF-\u03b2 receptors","volume":"1","author":"Stolzenburg","year":"2016","journal-title":"Biochem. J."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s00441-017-2697-6","article-title":"Microvesicle-mediated delivery of miR-1343: Impact on markers of fibrosis","volume":"371","author":"Stolzenburg","year":"2018","journal-title":"Cell Tissue Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/18\/4337\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:16:51Z","timestamp":1760188611000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/18\/4337"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,4]]},"references-count":152,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["ijms20184337"],"URL":"https:\/\/doi.org\/10.3390\/ijms20184337","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,4]]}}}