{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T01:50:05Z","timestamp":1778637005119,"version":"3.51.4"},"reference-count":59,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2008,7,9]],"date-time":"2008-07-09T00:00:00Z","timestamp":1215561600000},"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":[[2008,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The interaction between fibrogenic cells and extracellular matrix plays a role in liver fibrosis, yet the mechanisms are largely unknown. Secreted protein, acidic and rich in cysteine (SPARC) is a matricellular glycoprotein that is expressed by hepatic stellate cells and is overexpressed in fibrotic livers. We investigated the <jats:italic>in vivo<\/jats:italic> role of SPARC in experimentally induced liver fibrosis in rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A recombinant adenovirus carrying antisense SPARC was constructed (AdasSPARC). Advanced liver fibrosis was induced in Sprague\u2010Dawley rats by prolonged intraperitoneal administration of thioacetamide. Animals received injections of AdasSPARC or Ad\u03b2gal (control adenovirus) via the tail vein and directly into the liver 1 week after the first dose. The pathological changes in liver tissues and indices of fibrosis were assessed at eight weeks. Expression of SPARC, transforming growth factor (TGF)\u2010\u03b2 and \u03b1\u2010smooth muscle actin were evaluated by quantitative real\u2010time polymerase chain reaction, western blotting, enzyme\u2010linked immunosorbent assay and immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Hepatic SPARC expression significantly increased during the development of liver fibrosis. AdasSPARC markedly attenuated the development of hepatic fibrosis in rats treated with thiocetamide, as assessed by decreased collagen deposition, lower hepatic content of hydroxyproline and less advanced morphometric stage of fibrosis. AdasSPARC treatment reduced inflammatory activity (Knodell score) and suppressed transdifferentiation of hepatic stellate cell to the myofibroblasts like phenotype <jats:italic>in vivo<\/jats:italic>. Furthermore, <jats:italic>in vitro<\/jats:italic> inhibition of SPARC on hepatic stellate cells decreases the production of TGF\u2010\u03b2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This is the first study to demonstrate that knockdown of hepatic SPARC expression ameliorates thioacetamide\u2010induced liver fibrosis in rats with chronic liver injury. SPARC is a potential target for gene therapy in liver fibrosis. Copyright \u00a9 2008 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.1228","type":"journal-article","created":{"date-parts":[[2008,7,9]],"date-time":"2008-07-09T12:52:30Z","timestamp":1215607950000},"page":"993-1004","source":"Crossref","is-referenced-by-count":54,"title":["Adenovirus\u2010mediated inhibition of SPARC attenuates liver fibrosis in rats"],"prefix":"10.1002","volume":"10","author":[{"given":"Alejandra M.","family":"Camino","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catalina","family":"Atorrasagasti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Maccio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Prada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edgardo","family":"Salvatierra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Rizzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Alaniz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge B.","family":"Aquino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osvaldo. 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