Strategies for blocking the fibrogenic actions of connective tissue growth factor (CCN2): From pharmacological inhibition in vitro to targeted siRNA therapy in vivo

被引:61
作者
Brigstock, David R. [1 ,2 ]
机构
[1] Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA
[2] Ohio State Univ, Dept Surg, Div Pediat Surg, Columbus, OH 43212 USA
关键词
CCN2; Connective tissue growth factor; Transforming growth factor beta; TGF-beta; Gene transcription; Fibrogenesis; Fibrosis; Therapeutic; Anti-fibrotic; Antisense; Neutralizing; SiRNA; Hepatic fibrosis; CTGF;
D O I
10.1007/s12079-009-0043-9
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Connective tissue growth factor (CCN2) is a major pro-fibrotic factor that frequently acts downstream of transforming growth factor beta (TGF-beta)-mediated fibrogenic pathways. Much of our knowledge of CCN2 in fibrosis has come from studies in which its production or activity have been experimentally attenuated. These studies, performed both in vitro and in animal models, have demonstrated the utility of pharmacological inhibitors (e.g. tumor necrosis factor alpha (TNF-alpha), prostaglandins, peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists, statins, kinase inhibitors), neutralizing antibodies, antisense oligonucleotides, or small interfering RNA (siRNA) to probe the role of CCN2 in fibrogenic pathways. These investigations have allowed the mechanisms regulating CCN2 production to be more clearly defined, have shown that CCN2 is a rational anti-fibrotic target, and have established a framework for developing effective modalities of therapeutic intervention in vivo.
引用
收藏
页码:5 / 18
页数:14
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