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Báo cáo y học: "Attenuation of fibrosis in vitro and in vivo with SPARC siRNA"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: Attenuation of fibrosis in vitro and in vivo with SPARC siRNA. | Wang et al. Arthritis Research Therapy 2010 12 R60 http arthritis-research.eom content 12 2 R60 RESEARCH ARTICLE Open Access Attenuation of fibrosis in vitro and in vivo with SPARC siRNA Jiu-Cun Wang1 2 Syeling Lai3 Xinjian Guo2 Xuefeng Zhang2 Benoit de Crombrugghe4 Sonali Sonnylal4 FrankC Arnett2 and Xiaodong Zhou 2 Abstract Introduction SPARC is a matricellular protein which along with other extracellular matrix components including collagens is commonly over-expressed in fibrotic diseases. The purpose of this study was to examine whether inhibition of SPARC can regulate collagen expression in vitro and in vivo and subsequently attenuate fibrotic stimulation by bleomycin in mouse skin and lungs. Methods In in vitro studies skin fibroblasts obtained from a Tgfbrl knock-in mouse TBR1CA Cre-ER were transfected with SPARC siRNA. Gene and protein expressions of the Col1a2 and the Ctgf were examined by real-time RT-PCR and Western blotting respectively. In in vivo studies C57BL 6 mice were induced for skin and lung fibrosis by bleomycin and followed by SPARC siRNA treatment through subcutaneous injection and intratracheal instillation respectively. The pathological changes of skin and lungs were assessed by hematoxylin and eosin and Masson s trichrome stains. The expression changes of collagen in the tissues were assessed by real-time RT-PCR and non-crosslinked fibrillar collagen content assays. Results SPARC siRNA significantly reduced gene and protein expression of collagen type 1 in fibroblasts obtained from the TBR1CA Cre-ER mouse that was induced for constitutively active TGF-P receptor I. Skin and lung fibrosis induced by bleomycin was markedly reduced by treatment with SPARC siRNA. The anti-fibrotic effect of SPARC siRNA in vivo was accompanied by an inhibition of Ctgf expression in these same tissues. Conclusions Specific inhibition of SPARC effectively reduced fibrotic changes in vitro and in vivo. SPARC inhibition may represent a potential therapeutic .