{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T01:02:59Z","timestamp":1781658179994,"version":"3.54.5"},"reference-count":88,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:p>\n                    Hepatic stellate cells (HSCs) are the primary cell type responsible for liver fibrogenesis. Transforming growth factor beta 1 (TGF-\u03b21) and platelet-derived growth factor (PDGF) are key profibrotic cytokines that regulate HSC activation and proliferation with functional convergence. Dual RNA interference against their receptors may achieve therapeutic effects. A novel RNAi strategy based on HSC-specific\n                    <jats:italic toggle=\"yes\">GFAP<\/jats:italic>\n                    promoter-driven and lentiviral-expressed artificial microRNAs (amiRNAs) was devised that consists of an microRNA-30a backbone and effective shRNAs against mouse\n                    <jats:italic toggle=\"yes\">Pdgfr\u03b2<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">Tgfbr2<\/jats:italic>\n                    . Then, its antifibrotic efficacy was tested in primary and cultured HSCs and in mice affected with carbon tetrachloride\u2013induced hepatic fibrosis. The study shows that amiRNA-mediated\n                    <jats:italic toggle=\"yes\">Pdgfr\u03b2<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">Tgfbr2<\/jats:italic>\n                    co-silencing inhibits HSC activation and proliferation. After recombinant lentiviral particles were delivered into the liver via tail-vein injection, therapeutic amiRNAs were preferentially expressed in HSCs and efficiently co-knocked down\n                    <jats:italic toggle=\"yes\">in situ<\/jats:italic>\n                    <jats:italic toggle=\"yes\">Tgfbr2<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">Pdgfr\u03b2<\/jats:italic>\n                    expression, which correlates with downregulated expression of target or effector genes of their signaling, which include\n                    <jats:italic toggle=\"yes\">Pai-1<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">P70S6K<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">D-cyclins<\/jats:italic>\n                    . amiRNA-based HSC-specific co-silencing of\n                    <jats:italic toggle=\"yes\">Tgfbr2<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">Pdgfr\u03b2<\/jats:italic>\n                    significantly suppressed hepatic expression of fibrotic markers \u03b1-Sma and Col1a1, extracellular matrix regulators Mmps and Timp1, and phenotypically ameliorated liver fibrosis, as indicated by reductions in serum alanine aminotransferase activity, collagen deposition, and \u03b1-Sma-positive staining. The findings provide proof of concept for the use of amiRNA-mediated co-silencing of two profibrogenic pathways in liver fibrosis treatment and highlight the therapeutic potential of concatenated amiRNAs for gene therapy.\n                  <\/jats:p>","DOI":"10.1089\/hum.2018.047","type":"journal-article","created":{"date-parts":[[2018,7,19]],"date-time":"2018-07-19T08:38:34Z","timestamp":1531989514000},"page":"179-196","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Artificial MicroRNA-Mediated\n                    <i>Tgfbr2<\/i>\n                    and\n                    <i>Pdgfrb<\/i>\n                    Co-Silencing Ameliorates Carbon Tetrachloride\u2013Induced Hepatic Fibrosis in Mice"],"prefix":"10.1177","volume":"30","author":[{"given":"Yan","family":"Jiang","sequence":"first","affiliation":[{"name":"The Fifth People's Hospital of Shanghai, State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences of Shanghai Medical College, Fudan University, Shanghai, P.R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"The Fifth People's Hospital of Shanghai, State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences of Shanghai Medical College, Fudan University, Shanghai, P.R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuchu","family":"He","sequence":"additional","affiliation":[{"name":"The Fifth People's Hospital of Shanghai, State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences of Shanghai Medical College, Fudan University, Shanghai, P.R. China."},{"name":"State Key Laboratory of Proteomics, Beijing Institute of Radiation Medicine, Beijing, P.R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijian","family":"Wang","sequence":"additional","affiliation":[{"name":"The Fifth People's Hospital of Shanghai, State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences of Shanghai Medical College, Fudan University, Shanghai, P.R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,2,8]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28948"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.01.010"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3823"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-306842"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1571295"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.02.039"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13665"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.2741\/4090"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2015-309655"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/00042737-199812000-00009"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117497"},{"key":"e_1_3_3_13_2","first-page":"785","article-title":"Expression of platelet-derived growth factor and its receptors in normal human liver and during active hepatic fibrogenesis","volume":"148","author":"Pinzani M","year":"1996","unstructured":"Pinzani M, , Milani S, , Herbst H, et al. 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