{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T22:28:38Z","timestamp":1773872918152,"version":"3.50.1"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T00:00:00Z","timestamp":1594252800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T00:00:00Z","timestamp":1594252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"name":"the Guiding Projects of Hengyang City, 2018","award":["S2018F9031021273"],"award-info":[{"award-number":["S2018F9031021273"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Dig Dis Sci"],"published-print":{"date-parts":[[2021,6]]},"DOI":"10.1007\/s10620-020-06460-7","type":"journal-article","created":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T17:07:45Z","timestamp":1594314465000},"page":"1928-1939","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["MicroRNA-503 Targets Mothers Against Decapentaplegic Homolog 7 Enhancing Hepatic Stellate Cell Activation and Hepatic Fibrosis"],"prefix":"10.1007","volume":"66","author":[{"given":"Xia","family":"Xie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng-Yun","family":"Dou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0448-4503","authenticated-orcid":false,"given":"Hai-Bo","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,7,9]]},"reference":[{"key":"6460_CR1","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1097\/MOG.0b013e3283279668","volume":"25","author":"J Jiao","year":"2009","unstructured":"Jiao J, Friedman SL, Aloman C. Hepatic fibrosis. Curr Opin Gastroenterol. 2009;25:223\u2013229.","journal-title":"Curr Opin Gastroenterol"},{"key":"6460_CR2","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1172\/JCI24282","volume":"115","author":"R Bataller","year":"2005","unstructured":"Bataller R, Brenner DA. Liver fibrosis. J Clin Invest. 2005;115:209\u2013218.","journal-title":"J Clin Invest"},{"key":"6460_CR3","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1016\/j.jhep.2011.09.024","volume":"56","author":"EL Ellis","year":"2012","unstructured":"Ellis EL, Mann DA. Clinical evidence for the regression of liver fibrosis. J Hepatol. 2012;56:1171\u20131180.","journal-title":"J Hepatol"},{"key":"6460_CR4","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1002\/hep.27332","volume":"61","author":"E Seki","year":"2015","unstructured":"Seki E, Schwabe RF. Hepatic inflammation and fibrosis: functional links and key pathways. Hepatology. 2015;61:1066\u20131079.","journal-title":"Hepatology"},{"key":"6460_CR5","doi-asserted-by":"publisher","first-page":"2823","DOI":"10.1038\/ncomms3823","volume":"4","author":"I Mederacke","year":"2013","unstructured":"Mederacke I, Hsu CC, Troeger JS, et al. Fate tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology. Nat Commun. 2013;4:2823.","journal-title":"Nat Commun"},{"key":"6460_CR6","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1002\/cphy.c120035","volume":"3","author":"JE Puche","year":"2013","unstructured":"Puche JE, Saiman Y, Friedman SL. Hepatic stellate cells and liver fibrosis. Compr Physiol. 2013;3:1473\u20131492.","journal-title":"Compr Physiol"},{"key":"6460_CR7","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1136\/gutjnl-2014-306842","volume":"64","author":"YA Lee","year":"2015","unstructured":"Lee YA, Wallace MC, Friedman SL. Pathobiology of liver fibrosis: a translational success story. Gut. 2015;64:830\u2013841.","journal-title":"Gut"},{"key":"6460_CR8","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1016\/j.jhep.2010.02.005","volume":"52","author":"DA Mann","year":"2010","unstructured":"Mann DA, Marra F. Fibrogenic signalling in hepatic stellate cells. J Hepatol. 2010;52:949\u2013950.","journal-title":"J Hepatol"},{"key":"6460_CR9","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/S0168-8278(99)80010-5","volume":"30","author":"C Hellerbrand","year":"1999","unstructured":"Hellerbrand C, Stefanovic B, Giordano F, Burchardt ER, Brenner DA. The role of TGFbeta1 in initiating hepatic stellate cell activation in vivo. J Hepatol. 1999;30:77\u201387.","journal-title":"J Hepatol"},{"key":"6460_CR10","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1055\/s-2005-858989","volume":"44","author":"K Breitkopf","year":"2006","unstructured":"Breitkopf K, Godoy P, Ciuclan L, Singer MV, Dooley S. TGF-beta\/Smad signaling in the injured liver. Z Gastroenterol. 2006;44:57\u201366.","journal-title":"Z Gastroenterol"},{"key":"6460_CR11","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1152\/physrev.00013.2007","volume":"88","author":"SL Friedman","year":"2008","unstructured":"Friedman SL. Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol Rev. 2008;88:125\u2013172.","journal-title":"Physiol Rev"},{"key":"6460_CR12","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1369\/0022155415627681","volume":"64","author":"F Xu","year":"2016","unstructured":"Xu F, Liu C, Zhou D, Zhang L. TGF-beta\/SMAD pathway and its regulation in hepatic fibrosis. J Histochem Cytochem. 2016;64:157\u2013167.","journal-title":"J Histochem Cytochem"},{"key":"6460_CR13","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1038\/nrgastro.2013.87","volume":"10","author":"G Szabo","year":"2013","unstructured":"Szabo G, Bala S. MicroRNAs in liver disease. Nat Rev Gastroenterol Hepatol. 2013;10:542\u2013552.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"6460_CR14","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.cell.2007.12.024","volume":"132","author":"A Eulalio","year":"2008","unstructured":"Eulalio A, Huntzinger E, Izaurralde E. Getting to the root of miRNA-mediated gene silencing. Cell. 2008;132:9\u201314.","journal-title":"Cell"},{"key":"6460_CR15","doi-asserted-by":"publisher","first-page":"S313","DOI":"10.3816\/CLM.2009.s.030","volume":"9","author":"R Spizzo","year":"2009","unstructured":"Spizzo R, Rushworth D, Guerrero M, Calin GA. RNA inhibition, microRNAs, and new therapeutic agents for cancer treatment. Clin Lymphoma Myeloma. 2009;9:S313\u2013S318.","journal-title":"Clin Lymphoma Myeloma"},{"key":"6460_CR16","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1111\/liv.12660","volume":"35","author":"W Dai","year":"2015","unstructured":"Dai W, Zhao J, Tang N, et al. MicroRNA-155 attenuates activation of hepatic stellate cell by simultaneously preventing EMT process and ERK1 signalling pathway. Liver Int. 2015;35:1234\u20131243.","journal-title":"Liver Int"},{"key":"6460_CR17","doi-asserted-by":"publisher","first-page":"1378","DOI":"10.1016\/j.jhep.2016.01.035","volume":"64","author":"S Bala","year":"2016","unstructured":"Bala S, Csak T, Saha B, et al. The pro-inflammatory effects of miR-155 promote liver fibrosis and alcohol-induced steatohepatitis. J Hepatol. 2016;64:1378\u20131387.","journal-title":"J Hepatol"},{"key":"6460_CR18","doi-asserted-by":"publisher","first-page":"e0156111","DOI":"10.1371\/journal.pone.0156111","volume":"11","author":"SM Kweon","year":"2016","unstructured":"Kweon SM, Chi F, Higashiyama R, Lai K, Tsukamoto H. Wnt pathway stabilizes MeCP2 protein to repress PPAR-gamma in activation of hepatic stellate cells. PLoS ONE. 2016;11:e0156111.","journal-title":"PLoS ONE"},{"key":"6460_CR19","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.bbamcr.2017.10.011","volume":"1865","author":"Y Cai","year":"2018","unstructured":"Cai Y, Huang G, Ma L, et al. Smurf2, an E3 ubiquitin ligase, interacts with PDE4B and attenuates liver fibrosis through miR-132 mediated CTGF inhibition. Biochim Biophys Acta Mol Cell Res. 2018;1865:297\u2013308.","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"key":"6460_CR20","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1042\/CS20160334","volume":"130","author":"K Wu","year":"2016","unstructured":"Wu K, Ye C, Lin L, et al. Inhibiting miR-21 attenuates experimental hepatic fibrosis by suppressing both the ERK1 pathway in HSC and hepatocyte EMT. Clin Sci (Lond). 2016;130:1469\u20131480.","journal-title":"Clin Sci (Lond)"},{"key":"6460_CR21","doi-asserted-by":"publisher","first-page":"2414","DOI":"10.1002\/hep.29627","volume":"67","author":"JM Caviglia","year":"2018","unstructured":"Caviglia JM, Yan J, Jang MK, et al. MicroRNA-21 and Dicer are dispensable for hepatic stellate cell activation and the development of liver fibrosis. Hepatology. 2018;67:2414\u20132429.","journal-title":"Hepatology"},{"key":"6460_CR22","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1038\/s41419-018-0752-1","volume":"9","author":"L Ma","year":"2018","unstructured":"Ma L, Yang X, Wei R, et al. MicroRNA-214 promotes hepatic stellate cell activation and liver fibrosis by suppressing Sufu expression. Cell Death Dis. 2018;9:718.","journal-title":"Cell Death Dis"},{"key":"6460_CR23","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1016\/j.biopha.2017.05.142","volume":"92","author":"S Ge","year":"2017","unstructured":"Ge S, Xiong Y, Wu X, et al. Role of growth factor receptor-bound 2 in CCl4-induced hepatic fibrosis. Biomed Pharmacother. 2017;92:942\u2013951.","journal-title":"Biomed Pharmacother"},{"key":"6460_CR24","first-page":"918","volume":"15","author":"S Ge","year":"2016","unstructured":"Ge S, Zhang L, Xie J, et al. MicroRNA-146b regulates hepatic stellate cell activation via targeting of KLF4. Ann Hepatol. 2016;15:918\u2013928.","journal-title":"Ann Hepatol"},{"key":"6460_CR25","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.tox.2016.06.016","volume":"359\u2013360","author":"JJ Yang","year":"2016","unstructured":"Yang JJ, Liu LP, Tao H, et al. MeCP2 silencing of LncRNA H19 controls hepatic stellate cell proliferation by targeting IGF1R. Toxicology. 2016;359\u2013360:39\u201346.","journal-title":"Toxicology"},{"key":"6460_CR26","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.29528","author":"H He","year":"2019","unstructured":"He H, Dai J, Feng J et al. FBXO31 modulates activation of hepatic stellate cells and liver fibrogenesis by promoting ubiquitination of Smad7. J Cell Biochem. 2019. https:\/\/doi.org\/10.1002\/jcb.29528.","journal-title":"J Cell Biochem."},{"key":"6460_CR27","doi-asserted-by":"publisher","first-page":"2455","DOI":"10.1002\/jcb.25116","volume":"116","author":"S Ge","year":"2015","unstructured":"Ge S, Xie J, Liu F, He J, He J. MicroRNA-19b reduces hepatic stellate cell proliferation by targeting GRB2 in hepatic fibrosis models in vivo and in vitro as part of the inhibitory effect of estradiol. J Cell Biochem. 2015;116:2455\u20132464.","journal-title":"J Cell BiochemJ Cell Biochem"},{"key":"6460_CR28","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1007\/s10875-011-9647-y","volume":"32","author":"H Zhu","year":"2012","unstructured":"Zhu H, Li Y, Qu S, et al. MicroRNA expression abnormalities in limited cutaneous scleroderma and diffuse cutaneous scleroderma. J Clin Immunol. 2012;32:514\u2013522.","journal-title":"J Clin Immunol"},{"key":"6460_CR29","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1111\/jcmm.12754","volume":"20","author":"Y Zhou","year":"2016","unstructured":"Zhou Y, Deng L, Zhao D, et al. MicroRNA-503 promotes angiotensin II-induced cardiac fibrosis by targeting Apelin-13. J Cell Mol Med. 2016;20:495\u2013505.","journal-title":"J Cell Mol Med"},{"key":"6460_CR30","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1159\/000498875","volume":"44","author":"C Mann","year":"2019","unstructured":"Mann C, Kaistha BP, Kacik M, Stiewe T, Hoyer J. Downregulation of miR-503 in activated kidney fibroblasts disinhibits KCNN4 in an in vitro model of kidney fibrosis. Kidney Blood Press Res. 2019;44:113\u2013122.","journal-title":"Kidney Blood Press Res"},{"key":"6460_CR31","doi-asserted-by":"publisher","first-page":"11313","DOI":"10.1038\/s41598-017-11904-8","volume":"7","author":"W Yan","year":"2017","unstructured":"Yan W, Wu Q, Yao W, et al. MiR-503 modulates epithelial-mesenchymal transition in silica-induced pulmonary fibrosis by targeting PI3K p85 and is sponged by lncRNA MALAT1. Sci Rep. 2017;7:11313.","journal-title":"Sci Rep"},{"key":"6460_CR32","doi-asserted-by":"publisher","first-page":"285","DOI":"10.2147\/DDDT.S191617","volume":"13","author":"H Ren","year":"2019","unstructured":"Ren H, Li Y, Chen Y, Wang L. Endostatin attenuates PDGF-BB- or TGF-beta1-induced HSCs activation via suppressing RhoA\/ROCK1 signal pathways. Drug Des Devel Ther. 2019;13:285\u2013290.","journal-title":"Drug Des Devel Ther"},{"key":"6460_CR33","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1016\/j.tcb.2017.04.005","volume":"27","author":"EH Budi","year":"2017","unstructured":"Budi EH, Duan D, Derynck R. Transforming growth factor-beta receptors and smads: regulatory complexity and functional versatility. Trends Cell Biol. 2017;27:658\u2013672.","journal-title":"Trends Cell Biol"},{"key":"6460_CR34","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.1002\/hep.23186","volume":"50","author":"G Son","year":"2009","unstructured":"Son G, Hines IN, Lindquist J, Schrum LW, Rippe RA. Inhibition of phosphatidylinositol 3-kinase signaling in hepatic stellate cells blocks the progression of hepatic fibrosis. Hepatology. 2009;50:1512\u20131523.","journal-title":"Hepatology"},{"key":"6460_CR35","doi-asserted-by":"publisher","first-page":"2242","DOI":"10.1159\/000484303","volume":"43","author":"F Yu","year":"2017","unstructured":"Yu F, Chen B, Fan X, Li G, Dong P, Zheng J. Epigenetically-regulated microRNA-9-5p suppresses the activation of hepatic stellate cells via TGFBR1 and TGFBR2. Cell Physiol Biochem. 2017;43:2242\u20132252.","journal-title":"Cell Physiol Biochem"},{"key":"6460_CR36","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1002\/cbin.11022","volume":"42","author":"X Feili","year":"2018","unstructured":"Feili X, Wu S, Ye W, Tu J, Lou L. MicroRNA-34a-5p inhibits liver fibrosis by regulating TGF-beta1\/Smad3 pathway in hepatic stellate cells. Cell Biol Int. 2018;42:1370\u20131376.","journal-title":"Cell Biol Int"},{"key":"6460_CR37","doi-asserted-by":"publisher","first-page":"14327","DOI":"10.1038\/s41598-018-32309-1","volume":"8","author":"SA El-Wakeel","year":"2018","unstructured":"El-Wakeel SA, Rahmo RM, El-Abhar HS. Anti-fibrotic impact of Carvedilol in a CCl-4 model of liver fibrosis via serum microRNA-200a\/SMAD7 enhancement to bridle TGF-beta1\/EMT track. Sci Rep. 2018;8:14327.","journal-title":"Sci Rep"},{"key":"6460_CR38","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1053\/j.gastro.2008.04.038","volume":"135","author":"S Dooley","year":"2008","unstructured":"Dooley S, Hamzavi J, Ciuclan L, et al. Hepatocyte-specific Smad7 expression attenuates TGF-beta-mediated fibrogenesis and protects against liver damage. Gastroenterology. 2008;135:642\u2013659.","journal-title":"Gastroenterology"},{"key":"6460_CR39","doi-asserted-by":"publisher","first-page":"2130","DOI":"10.1111\/j.1582-4934.2008.00262.x","volume":"12","author":"J Hamzavi","year":"2008","unstructured":"Hamzavi J, Ehnert S, Godoy P, et al. Disruption of the Smad7 gene enhances CCI4-dependent liver damage and fibrogenesis in mice. J Cell Mol Med. 2008;12:2130\u20132144.","journal-title":"J Cell Mol Med"},{"key":"6460_CR40","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.toxlet.2013.10.038","volume":"224","author":"EB Bian","year":"2014","unstructured":"Bian EB, Huang C, Wang H, et al. Repression of Smad7 mediated by DNMT1 determines hepatic stellate cell activation and liver fibrosis in rats. Toxicol Lett. 2014;224:175\u2013185.","journal-title":"Toxicol Lett"},{"key":"6460_CR41","first-page":"25","volume":"64","author":"P Trivedi","year":"1983","unstructured":"Trivedi P, Mowat AP. Carbon tetrachloride-induced hepatic fibrosis and cirrhosis in the developing rat: an experimental model of cirrhosis in childhood. Br J Exp Pathol. 1983;64:25\u201333.","journal-title":"Br J Exp Pathol"}],"container-title":["Digestive Diseases and Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10620-020-06460-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10620-020-06460-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10620-020-06460-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T23:41:56Z","timestamp":1625787716000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10620-020-06460-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,9]]},"references-count":41,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["6460"],"URL":"https:\/\/doi.org\/10.1007\/s10620-020-06460-7","relation":{},"ISSN":["0163-2116","1573-2568"],"issn-type":[{"value":"0163-2116","type":"print"},{"value":"1573-2568","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,9]]},"assertion":[{"value":"15 April 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 June 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"The authors declare that they have no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}