Adenovirus-mediated inhibition of SPARC attenuates liver fibrosis in rats

摘要: Background The interaction between fibrogenic cells and extracellular matrix plays a role in liver fibrosis, yet the mechanisms are largely unknown. Secreted protein, acidic rich cysteine (SPARC) is matricellular glycoprotein that expressed by hepatic stellate overexpressed fibrotic livers. We investigated vivo of SPARC experimentally induced fibrosis rats. Methods A recombinant adenovirus carrying antisense was constructed (AdasSPARC). Advanced Sprague-Dawley rats prolonged intraperitoneal administration thioacetamide. Animals received injections AdasSPARC or Adβgal (control adenovirus) via tail vein directly into 1 week after first dose. The pathological changes tissues indices were assessed at eight weeks. Expression SPARC, transforming growth factor (TGF)-β α-smooth muscle actin evaluated quantitative real-time polymerase chain reaction, western blotting, enzyme-linked immunosorbent assay immunohistochemistry. Results Hepatic expression significantly increased during development fibrosis. markedly attenuated treated with thiocetamide, as decreased collagen deposition, lower content hydroxyproline less advanced morphometric stage treatment reduced inflammatory activity (Knodell score) suppressed transdifferentiation cell to myofibroblasts like phenotype vivo. Furthermore, vitro inhibition on decreases production TGF-β. Conclusions This study demonstrate knockdown ameliorates thioacetamide-induced chronic injury. potential target for gene therapy Copyright © 2008 John Wiley & Sons, Ltd.