{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T03:21:50Z","timestamp":1772594510327,"version":"3.50.1"},"reference-count":43,"publisher":"Portland Press Ltd.","issue":"16","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,8,1]]},"abstract":"<jats:p>MicroRNA-21 (miR-21) has emerged as a critical regulatory molecule and an important serum marker in hepatic fibrogenesis. The aim of the present study was to investigate the role of inhibiting miR-21 on hepatic fibrosis treatment. Serum miR-21 levels in 60 healthy individuals and 180 patients with different stages of liver cirrhosis were examined, miR-21 levels in normal or cirrhotic human liver tissues (n=10 each) were also detected. An adenoviral vector (Ad-TuD-21) carrying the sponging ToughDecoy (TuD)-RNA sequence against miR-21 was constructed to reduce miR-21 expression efficiently in\u00a0vitro and in\u00a0vivo. Histological and immunohistological examinations were performed to evaluate the inhibitory effects and mechanism of Ad-TuD-21 delivery into carbon tetrachloride (CCl4) induced hepatic fibrosis rats by targeting extracellular signal-regulated kinase 1 (ERK1) signalling in hepatic stellate cells (HSC) and hepatocyte epithelial\u2013mesenchymal transition (EMT). Our results revealed that enhanced miR-21 levels in cirrhotic patients were related to the severity and activity of liver cirrhosis. Ad-TuD-21 administered to liver fibrosis rats could remarkably suppress profibrotic gene expression, cause histological improvements in liver and attenuate hepatic fibrosis significantly. More importantly, after Ad-TuD-21 treatment, inhibition of both the ERK1 signalling pathway in HSC and hepatocyte EMT was confirmed, which paralleled the enhancement of miR-21 target genes\u2013sprouty2 (SPRY2) and hepatocyte nuclear factor 4\u03b1 (HNF4\u03b1)\u2013expression in\u00a0vivo. These data demonstrated that miR-21 is a key regulator to promote hepatic fibrogenesis, and sponging miR-21 expression may present a novel potentially therapeutic option for hepatic fibrosis.<\/jats:p>","DOI":"10.1042\/cs20160334","type":"journal-article","created":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T03:08:27Z","timestamp":1464232107000},"page":"1469-1480","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Inhibiting <i>miR-21<\/i> attenuates experimental hepatic fibrosis by suppressing both the ERK1 pathway in HSC and hepatocyte EMT"],"prefix":"10.1042","volume":"130","author":[{"given":"Kaiming","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changhong","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yimin","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Endoscopy, Shanghai Tongren Hospital, Shanghai 200336, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiping","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China"},{"name":"Department of Endoscopy, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2016,7,7]]},"reference":[{"key":"2021113010422023000_B1","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1053\/j.gastro.2008.03.003","article-title":"Mechanisms of hepatic fibrogenesis","volume":"134","author":"Friedman","year":"2008","journal-title":"Gastroenterology"},{"key":"2021113010422023000_B2","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1146\/annurev-pathol-011110-130246","article-title":"Pathogenesis of liver fibrosis","volume":"6","author":"Hernandez-Gea","year":"2011","journal-title":"Annu. 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