Strategies for blocking the fibrogenic actions of connective tissue growth factor (CCN2): From pharmacological inhibition in vitro to targeted siRNA therapy in vivo.
Strategies for blocking the fibrogenic actions of connective tissue growth factor (CCN2): From pharmacological inhibition in vitro to targeted siRNA therapy in vivo.
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DOI：
10.1007/s12079-009-0043-9
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发表时间：
2009-03
影响因子：
4.1
通讯作者：
Brigstock, David R.
中科院分区：
文献类型：
--
作者：
Brigstock, David R.
关键词：
结缔组织生长因子（CCN 2）是一种主要的促纤维化因子，其经常在转化生长因子β（TGF-β）介导的纤维化途径的下游起作用。我们对纤维化中CCN 2的大部分了解都来自于实验性减弱其产生或活性的研究。这些在体外和动物模型中进行的研究已经证明了药理学抑制剂（例如肿瘤坏死因子α（TNF-α）、阿糖胞苷、过氧化物酶体增殖物激活受体-γ（PPAR-γ）激动剂、他汀类药物、激酶抑制剂）、中和抗体、反义寡核苷酸或小干扰RNA（siRNA）在探测CCN 2在纤维化途径中的作用方面的效用。这些研究使得调节CCN 2产生的机制得到更清楚的定义，表明CCN 2是合理的抗纤维化靶点，并建立了开发有效的体内治疗干预模式的框架。
Connective tissue growth factor (CCN2) is a major pro-fibrotic factor that frequently acts downstream of transforming growth factor beta (TGF-β)-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-α), prostaglandins, peroxisome proliferator-activated receptor-gamma (PPAR-γ) 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.
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