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转化生长因子-β:抗狭窄治疗的一个有前景的靶点。

Transforming growth factor-beta: a promising target for anti-stenosis therapy.

作者信息

Chamberlain J

机构信息

Cardiovascular Research Group, Section of Medicine, University of Sheffield, Clinical Sciences Centre, Northern General Hospital, Herries Road, Sheffield, S5 7AU, UK.

出版信息

Cardiovasc Drug Rev. 2001 Winter;19(4):329-44. doi: 10.1111/j.1527-3466.2001.tb00074.x.

Abstract

Transforming growth factor-beta (TGF-beta) is the general name for a family of cytokines which have widespread effects on many aspects of growth and development. The TGF-beta isoforms are produced by most cell types and exert a wide range of effects in a context-dependent autocrine, paracrine or endocrine fashion via interactions with distinct receptors on the cell surface. TGF-beta is involved in the wound healing process and, thus plays a significant role in the formation of a restenotic lesion after percutaneous transluminal coronary angioplasty (PTCA) or stenting. Perhaps because of its wide-ranging effects, TGF-beta is usually released from cells in a latent form, and its activation and signaling are complex. Manipulation of the TGF-beta1, TGF-beta2, and TGF-beta3 isoforms by inhibiting their expression, activation, or signaling reduces scarring and fibrosis in animal models. However, to date, few have reached clinical trial. This review summarizes current knowledge on the activation and signaling of TGF-beta, and focuses on the anti-TGF-beta strategies which may lead to clinical applications in the prevention of restenosis following PTCA or stenting.

摘要

转化生长因子-β(TGF-β)是一类细胞因子的统称,它们在生长和发育的许多方面都具有广泛的作用。大多数细胞类型都会产生TGF-β亚型,这些亚型通过与细胞表面不同受体相互作用,以自分泌、旁分泌或内分泌的方式,在依赖于环境的情况下发挥广泛的作用。TGF-β参与伤口愈合过程,因此在经皮腔内冠状动脉成形术(PTCA)或支架置入术后再狭窄病变的形成中起重要作用。也许是由于其广泛的作用,TGF-β通常以潜伏形式从细胞中释放出来,其激活和信号传导过程较为复杂。在动物模型中,通过抑制TGF-β1、TGF-β2和TGF-β3亚型的表达、激活或信号传导来调控它们,可减少瘢痕形成和纤维化。然而,迄今为止,很少有相关研究进入临床试验阶段。本综述总结了目前关于TGF-β激活和信号传导的知识,并重点关注可能在PTCA或支架置入术后预防再狭窄的临床应用中发挥作用的抗TGF-β策略。

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