Attenuation of fibrosis in vitro and in vivo with SPARC siRNA.
Attenuation of fibrosis in vitro and in vivo with SPARC siRNA.
复制标题
使用 SPARC siRNA 在体外和体内减弱纤维化
DOI：
10.1186/ar2973
复制
发表时间：
2010
影响因子：
4.9
通讯作者：
Zhou X
中科院分区：
文献类型：
--
作者：
Wang JC;Lai S;Guo X;Zhang X;de Crombrugghe B;Sonnylal S;Arnett FC;Zhou X
介绍
细胞外基质是一种基质细胞蛋白，其沿着其他细胞外基质组分，包括胶原蛋白，通常在纤维化疾病中过表达。本研究的目的是检查抑制BLM是否可以在体外和体内调节胶原蛋白的表达，并随后减弱博莱霉素对小鼠皮肤和肺的纤维化刺激。
方法
在体外研究中，将从Tgfbr 1敲入小鼠（TBR 1CA; Cre-ER）获得的皮肤成纤维细胞用siRNA转染。实时荧光定量RT-PCR和Western blotting分别检测Col 1a 2和Ctgf基因和蛋白的表达。在体内研究中，通过博来霉素诱导C57 BL/6小鼠的皮肤和肺纤维化，然后分别通过皮下注射和腹膜内滴注进行siRNA治疗。HE染色和Masson三色染色观察皮肤和肺脏的病理变化。通过实时定量RT-PCR和非交联纤维胶原含量测定来评估组织中胶原表达的变化。
结果
在从诱导组成型活性TGF-β受体I的TBR 1CA; Cre-ER小鼠获得的成纤维细胞中，siRNA显著降低了1型胶原蛋白的基因和蛋白表达。博来霉素诱导的皮肤和肺纤维化通过用siRNA治疗显著减少。在体内的抗纤维化作用的siRNA是伴随着在这些相同的组织中的Ctgf表达的抑制。
结论
在体外和体内，特异性抑制纤维化可有效减少纤维化变化。纤维化抑制可能代表纤维化疾病的潜在治疗方法。
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 Tgfbr1 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-β 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 approach to fibrotic diseases.
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影响因子：
7.7
作者：
Kos K;Wong S;Tan B;Gummesson A;Jernas M;Franck N;Kerrigan D;Nystrom FH;Carlsson LM;Randeva HS;Pinkney JH;Wilding JP
通讯作者：
Wilding JP
影响因子：
4
作者：
Francki, A;McClure, TD;Sage, EH
通讯作者：
Sage, EH
影响因子：
5.5
作者：
Davies, C. A.;Jeziorska, M.;Herrick, A. L.
通讯作者：
Herrick, A. L.
影响因子：
6
作者：
Socha, Matthew J.;Manhiani, Marlina;Motamed, Kouros
通讯作者：
Motamed, Kouros
DOI：
10.1038/nrd2310
发表时间：
2007-06
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
de Fougerolles A;Vornlocher HP;Maraganore J;Lieberman J
通讯作者：
Lieberman J