{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T03:35:23Z","timestamp":1773545723542,"version":"3.50.1"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81102268,81471615"],"award-info":[{"award-number":["81102268,81471615"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"13th Five-Year National Science and Technology Major Project for New Drugs of\u2002the\u2002Ministry\u2002of\u2002Science\u2002and\u2002Technology\u2002of\u2002China","award":["2019ZX09734001-002-004"],"award-info":[{"award-number":["2019ZX09734001-002-004"]}]},{"name":"Chinese National Key Technology R&D Program of Ministry of Science and Technology","award":["2017YFC0907604"],"award-info":[{"award-number":["2017YFC0907604"]}]},{"name":"Medical and health science and technology innovation project of Chinese Academy of Medical Sciences","award":["2019-I2M-2-008"],"award-info":[{"award-number":["2019-I2M-2-008"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Systemic sclerosis (SSc) is an acquired autoimmune disorder characterized by excessive accumulation of collagen and progressive tissue fibrosis. Although interstitial lung disease (ILD) complicates the majority of SSc patients and is the leading cause of death, its pathogenesis remains largely unclear. In the current study, we aimed to evaluate the role of microRNAs in SSc-ILD.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>miRNA expression patterns were assessed by miRNA array and real-time PCR from serum and PBMCs of SSc-ILD patients and healthy controls. Bleomycin-induced SSc-ILD mouse model was used to verify the miRNA expression in the lung tissue. The function of miRNAs in pulmonary fibroblasts was assessed using miRNA inhibitors, and mimics.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>miR-320a was significantly downregulated in both SSc-ILD patients and mouse models. The inhibition or overexpression of miR-320a in human pulmonary fibroblasts significantly affected the protein expression of type I collagen. Luciferase reporter assay, RT-PCR, and western blot analysis identified TGFBR2 and IGF1R as direct targets of miR-320a. Upon TGF-\u03b2 stimulation, the expression of miR-320a and collagen genes were significantly upregulated.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>miR-320a, together with its target genes, TGFBR2 and IGF1R, constituted a complex regulatory network, and played an important role in the fibrotic process of SSc-ILD. Investigation of more detailed mechanisms of miR-320a-mediated regulation of collagen expression may provide new therapeutic strategies for SSc-ILD.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13075-020-02411-9","type":"journal-article","created":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T19:14:27Z","timestamp":1610392467000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["MicroRNA-320a: an important regulator in the fibrotic process in interstitial lung disease of systemic sclerosis"],"prefix":"10.1186","volume":"23","author":[{"given":"Yiqun","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaojun","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaxin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chanyuan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiuliang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengtao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofeng","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changzheng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4541-9898","authenticated-orcid":false,"given":"Qian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"issue":"12 Pt 2","key":"2411_CR1","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1016\/S0755-4982(06)74924-7","volume":"35","author":"A Servettaz","year":"2006","unstructured":"Servettaz A, Agard C, Tamby MC, Guilpain P, Guillevin L, Mouthon L. Systemic sclerosis: pathophysiology of a multifaceted disease. Presse Med. 2006;35(12 Pt 2):1903\u201315.","journal-title":"Presse Med"},{"issue":"3","key":"2411_CR2","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/S1568-9972(03)00004-1","volume":"2","author":"MC Tamby","year":"2003","unstructured":"Tamby MC, Chanseaud Y, Guillevin L, Mouthon L. New insights into the pathogenesis of systemic sclerosis. Autoimmun Rev. 2003;2(3):152\u20137.","journal-title":"Autoimmun Rev"},{"issue":"7","key":"2411_CR3","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1136\/ard.2006.066068","volume":"66","author":"VD Steen","year":"2007","unstructured":"Steen VD, Medsger TA. Changes in causes of death in systemic sclerosis, 1972-2002. Ann Rheum Dis. 2007;66(7):940\u20134.","journal-title":"Ann Rheum Dis"},{"issue":"2","key":"2411_CR4","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","volume":"116","author":"DP Bartel","year":"2004","unstructured":"Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281\u201397.","journal-title":"Cell."},{"issue":"11","key":"2411_CR5","doi-asserted-by":"crossref","first-page":"102396","DOI":"10.1016\/j.autrev.2019.102396","volume":"18","author":"TW Henry","year":"2019","unstructured":"Henry TW, Mendoza FA, Jimenez SA. Role of microRNA in the pathogenesis of systemic sclerosis tissue fibrosis and vasculopathy. Autoimmun Rev. 2019;18(11):102396.","journal-title":"Autoimmun Rev"},{"issue":"2","key":"2411_CR6","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1139\/bcb-2014-0095","volume":"93","author":"L Cushing","year":"2015","unstructured":"Cushing L, Kuang P, Lu J. The role of miR-29 in pulmonary fibrosis. Biochem Cell Biol. 2015;93(2):109\u201318.","journal-title":"Biochem Cell Biol"},{"key":"2411_CR7","doi-asserted-by":"crossref","first-page":"8319283","DOI":"10.1155\/2016\/8319283","volume":"2016","author":"A Loboda","year":"2016","unstructured":"Loboda A, Sobczak M, Jozkowicz A, Dulak J. TGF-beta1\/Smads and miR-21 in renal fibrosis and inflammation. Mediat Inflamm. 2016;2016:8319283.","journal-title":"Mediat Inflamm"},{"issue":"5","key":"2411_CR8","first-page":"1415","volume":"33","author":"L Chi","year":"2019","unstructured":"Chi L, Xiao Y, Zhu L, Zhang M, Xu B, Xia H, et al. microRNA-155 attenuates profibrotic effects of transforming growth factor-beta on human lung fibroblasts. J Biol Regul Homeost Agents. 2019;33(5):1415\u201324.","journal-title":"J Biol Regul Homeost Agents"},{"issue":"3","key":"2411_CR9","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1002\/1529-0131(200103)44:3<735::AID-ANR125>3.0.CO;2-F","volume":"44","author":"LS Lonzetti","year":"2001","unstructured":"Lonzetti LS, Joyal F, Raynauld JP, Roussin A, Goulet JR, Rich E, et al. Updating the American College of Rheumatology preliminary classification criteria for systemic sclerosis: addition of severe nailfold capillaroscopy abnormalities markedly increases the sensitivity for limited scleroderma. Arthritis Rheum. 2001;44(3):735\u20136.","journal-title":"Arthritis Rheum"},{"key":"2411_CR10","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.canlet.2017.03.004","volume":"397","author":"Z Zhang","year":"2017","unstructured":"Zhang Z, Li X, Sun W, Yue S, Yang J, Li J, et al. Loss of exosomal miR-320a from cancer-associated fibroblasts contributes to HCC proliferation and metastasis. Cancer Lett. 2017;397:33\u201342.","journal-title":"Cancer Lett"},{"issue":"10","key":"2411_CR11","doi-asserted-by":"crossref","first-page":"842","DOI":"10.4251\/wjgo.v11.i10.842","volume":"11","author":"YS Li","year":"2019","unstructured":"Li YS, Zou Y, Dai DQ. MicroRNA-320a suppresses tumor progression by targeting PBX3 in gastric cancer and is downregulated by DNA methylation. World J Gastrointest Oncol. 2019;11(10):842\u201356.","journal-title":"World J Gastrointest Oncol"},{"key":"2411_CR12","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.3389\/fimmu.2018.02711","volume":"9","author":"D Beuzelin","year":"2018","unstructured":"Beuzelin D, Kaeffer B. Exosomes and miRNA-loaded biomimetic nanovehicles, a focus on their potentials preventing type-2 diabetes linked to metabolic syndrome. Front Immunol. 2018;9:2711.","journal-title":"Front Immunol"},{"issue":"10","key":"2411_CR13","doi-asserted-by":"crossref","first-page":"3055","DOI":"10.18632\/aging.101962","volume":"11","author":"M He","year":"2019","unstructured":"He M, Wang J, Yin Z, Zhao Y, Hou H, Fan J, et al. MiR-320a induces diabetic nephropathy via inhibiting MafB. Aging (Albany NY). 2019;11(10):3055\u201379.","journal-title":"Aging (Albany NY)"},{"issue":"18","key":"2411_CR14","first-page":"5828","volume":"22","author":"HX Zhang","year":"2018","unstructured":"Zhang HX, Sun C, Yu HC, Song B, Pan ZX. Targeted inhibition of beta-catenin by miR-320 and decreased MMP-13 expression in suppressing chondrocyte collagen degradation. Eur Rev Med Pharmacol Sci. 2018;22(18):5828\u201335.","journal-title":"Eur Rev Med Pharmacol Sci"},{"issue":"5","key":"2411_CR15","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/j.joca.2015.12.012","volume":"24","author":"F Meng","year":"2016","unstructured":"Meng F, Zhang Z, Chen W, Huang G, He A, Hou C, et al. MicroRNA-320 regulates matrix metalloproteinase-13 expression in chondrogenesis and interleukin-1beta-induced chondrocyte responses. Osteoarthr Cartil. 2016;24(5):932\u201341.","journal-title":"Osteoarthr Cartil"},{"issue":"4","key":"2411_CR16","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1073\/pnas.85.4.1105","volume":"85","author":"RP Penttinen","year":"1988","unstructured":"Penttinen RP, Kobayashi S, Bornstein P. Transforming growth factor beta increases mRNA for matrix proteins both in the presence and in the absence of changes in mRNA stability. Proc Natl Acad Sci U S A. 1988;85(4):1105\u20138.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"2411_CR17","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nrrheum.2014.128","volume":"10","author":"JC Broen","year":"2014","unstructured":"Broen JC, Radstake TR, Rossato M. The role of genetics and epigenetics in the pathogenesis of systemic sclerosis. Nat Rev Rheumatol. 2014;10(11):671\u201381.","journal-title":"Nat Rev Rheumatol"},{"issue":"2","key":"2411_CR18","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1161\/HYPERTENSIONAHA.117.10094","volume":"71","author":"R Verjans","year":"2018","unstructured":"Verjans R, Peters T, Beaumont FJ, van Leeuwen R, van Herwaarden T, Verhesen W, et al. MicroRNA-221\/222 family counteracts myocardial fibrosis in pressure overload-induced heart failure. Hypertension. 2018;71(2):280\u20138.","journal-title":"Hypertension."},{"issue":"11","key":"2411_CR19","doi-asserted-by":"crossref","first-page":"11269","DOI":"10.1007\/s13277-014-2283-4","volume":"35","author":"T Guo","year":"2014","unstructured":"Guo T, Feng Y, Liu Q, Yang X, Jiang T, Chen Y, et al. MicroRNA-320a suppresses in GBM patients and modulates glioma cell functions by targeting IGF-1R. Tumour Biol. 2014;35(11):11269\u201375.","journal-title":"Tumour Biol"},{"issue":"1","key":"2411_CR20","doi-asserted-by":"crossref","first-page":"4567","DOI":"10.1038\/s41467-019-12564-0","volume":"10","author":"J Li","year":"2019","unstructured":"Li J, Choi E, Yu H, Bai XC. Structural basis of the activation of type 1 insulin-like growth factor receptor. Nat Commun. 2019;10(1):4567.","journal-title":"Nat Commun"},{"issue":"5 Pt 1","key":"2411_CR21","first-page":"1626","volume":"158","author":"ST Uh","year":"1998","unstructured":"Uh ST, Inoue Y, King TE Jr, Chan ED, Newman LS, Riches DW. Morphometric analysis of insulin-like growth factor-I localization in lung tissues of patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 1998;158(5 Pt 1):1626\u201335.","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"2411_CR22","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/1755-1536-6-16","volume":"6","author":"L Honeyman","year":"2013","unstructured":"Honeyman L, Bazett M, Tomko TG, Haston CK. MicroRNA profiling implicates the insulin-like growth factor pathway in bleomycin-induced pulmonary fibrosis in mice. Fibrogenesis Tissue Repair. 2013;6(1):16.","journal-title":"Fibrogenesis Tissue Repair"},{"issue":"4","key":"2411_CR23","doi-asserted-by":"crossref","first-page":"5363","DOI":"10.1096\/fj.201901719RR","volume":"34","author":"DM Hernandez","year":"2020","unstructured":"Hernandez DM, Kang JH, Choudhury M, Andrianifahanana M, Yin X, Limper AH, et al. IPF pathogenesis is dependent upon TGFbeta induction of IGF-1. FASEB J. 2020;34(4):5363\u201388.","journal-title":"FASEB J"}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-020-02411-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13075-020-02411-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13075-020-02411-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T19:59:14Z","timestamp":1610395154000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/s13075-020-02411-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,11]]},"references-count":23,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2411"],"URL":"https:\/\/doi.org\/10.1186\/s13075-020-02411-9","relation":{},"ISSN":["1478-6362"],"issn-type":[{"value":"1478-6362","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,11]]},"assertion":[{"value":"2 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was approved by the medical ethics committee of Peking Union Medical College Hospital (PUMCH) and the ethics committee of the European League Against Rheumatism Scleroderma Trial and Research Group (EUSTAR). The procedures for care and use of animals were approved by the animal experimentation ethics committee of PUMCH.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no conflicts of interest to any part of this manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"21"}}