{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T10:59:10Z","timestamp":1698663550871},"reference-count":46,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2005,3,17]],"date-time":"2005-03-17T00:00:00Z","timestamp":1111017600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2005,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background\/aims<\/jats:title><jats:p>Transforming growth factor \u03b2 (TGF\u03b21) is considered the key mediator in the process of liver fibrosis. The purpose of this investigation was to evaluate the activity of ribozymes against TGF\u03b21 in a cell\u2010free system and activated hepatic stellate cells (HSCs), and antifibrotic effect in activated HSCs <jats:italic>in vitro<\/jats:italic> and in rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Three ribozymes targeting against TGF\u03b21 mRNA were designed, and then cloned into the U1 snRNA expression cassette. The chimeric ribozymes were selected for the analysis of their performances in activated HSCs through the detection of their cleavage activities in a cell\u2010free system. After ribozyme\u2010encoding plasmids had been transfected into HSC\u2010T6 cells, the effects of ribozymes on activated HSCs were evaluated through the analysis of proliferation, activation and collagen deposition of HSC\u2010T6. The adenoviral vector expressing the ribozymes was constructed, and then delivered into rat models of hepatic fibrosis induced by carbon tetrachloride.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TGF\u03b21 expression was efficiently down\u2010regulated in activated HSCs by U1 snRNA chimeric ribozymes which possessed perfect cleavage activity in a cell\u2010free system. Further studies demonstrated that U1 snRNA chimeric ribozymes inhibited the synthesis of collagen I, reduced deposition of collagen I, suppressed BrdU incorporation, but had no effect on desmin and \u03b1\u2010SMA expression in transfected HSC\u2010T6 cells. Histological analysis demonstrated that the adenoviral vector expressing ribozyme (Rz803) could alleviate fibrotic pathology in rats treated with carbon tetrachloride.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The anti\u2010TGF\u03b21 ribozymes could reverse the character of activated HSCs <jats:italic>in vitro<\/jats:italic> and improve fibrotic pathology <jats:italic>in vivo<\/jats:italic>. It indicated that TGF\u03b21 could be considered as a novel candidate for a therapeutic agent against hepatic fibrosis. Copyright \u00a9 2005 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.744","type":"journal-article","created":{"date-parts":[[2005,3,17]],"date-time":"2005-03-17T10:46:31Z","timestamp":1111056391000},"page":"965-976","source":"Crossref","is-referenced-by-count":9,"title":["Ribozymes against TGF\u03b21 reverse character of activated hepatic stellate cells <i>in vitro<\/i> and inhibit liver fibrosis in 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