{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:05:16Z","timestamp":1792065916573,"version":"4.4.0"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":139,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"he National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81430051"],"award-info":[{"award-number":["81430051"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The National Basic Research Program (973 Program)","award":["2007CB513100"],"award-info":[{"award-number":["2007CB513100"]}]},{"name":"the National Institutes of Health to G.G.","award":["UL1RR031982"],"award-info":[{"award-number":["UL1RR031982"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:p>Schistosomiasis is a serious parasitic disease in humans, which can lead to liver fibrosis and death. Accumulating evidence indicated that targeting the deregulated microRNAs (miRNAs) could mitigate disease outcomes. Here, we showed that progressive hepatic schistosomiasis caused elevation of miR\u201021 and efficient and sustained inhibition of miR\u201021 by using highly hepatic tropic adeno\u2010associated virus serotype 8 (rAAV8), which protected mice against lethal schistosome infection through attenuation of hepatic fibrosis (HF). We demonstrated an additive role of interleukin (IL)\u221213 and transforming growth factor beta 1 (TGF\u2010\u03b21) in up\u2010regulating miR\u201021 expression in hepatic stellate cells (HSCs) by activation of mothers against decapentaplegic (SMAD) proteins. Furthermore, down\u2010regulation of miR\u201021 in HSCs reversed HF by enhancing SMAD7 expression, thus repressing TGF\u2010\u03b21\/Smad and IL\u201013\/Smad pathways. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: This study suggests the mechanism of IL\u201013\u2010mediated schistosomiasis HF by up\u2010regulation of miR\u201021 and highlights the potential of rAAV8\u2010mediated miR\u201021 inhibition as a therapeutic intervention for hepatic fibrotic diseases, such as schistosomiasis. (H<jats:sc>epatology<\/jats:sc> 2015;61:2008\u20132017)<\/jats:p>","DOI":"10.1002\/hep.27671","type":"journal-article","created":{"date-parts":[[2014,12,24]],"date-time":"2014-12-24T23:25:29Z","timestamp":1419463529000},"page":"2008-2017","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":70,"title":["Recombinant adeno\u2010associated virus\u2013mediated inhibition of microRNA\u201021 protects mice against the lethal schistosome infection by repressing both IL\u201013 and transforming growth factor beta 1 pathways"],"prefix":"10.1097","volume":"61","author":[{"given":"Xing","family":"He","sequence":"first","affiliation":[{"name":"Department of Tropical Infectious Diseases,Second Military Medical University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Xie","sequence":"additional","affiliation":[{"name":"Gene Therapy Center,University of Massachusetts Medical School,Worcester,MA"},{"name":"Department of Microbiology and Physiology Systems,University of Massachusetts Medical School,Worcester,MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Tropical Infectious Diseases,Second Military Medical University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Su","sequence":"additional","affiliation":[{"name":"Gene Therapy Center,University of Massachusetts Medical School,Worcester,MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Sai","sequence":"additional","affiliation":[{"name":"Department of Tropical Infectious Diseases,Second Military Medical University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruipu","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Tropical Infectious Diseases,Second Military Medical University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Tropical Infectious Diseases,Second Military Medical University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xufeng","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Tropical Infectious Diseases,Second Military Medical University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangping","family":"Gao","sequence":"additional","affiliation":[{"name":"Gene Therapy Center,University of Massachusetts Medical School,Worcester,MA"},{"name":"Department of Microbiology and Physiology Systems,University of Massachusetts Medical School,Worcester,MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqing","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Tropical Infectious 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