Dental Sciences Building, London ON N6A 5C1, Canada.
Circ Res. 2010 Jun 11;106(11):1675-80. doi: 10.1161/CIRCRESAHA.110.217737.
Fibrosis is one of the largest groups of diseases for which there is no therapy but is believed to occur because of a persistent tissue repair program. During connective tissue repair, "activated" fibroblasts migrate into the wound area, where they synthesize and remodel newly created extracellular matrix. The specialized type of fibroblast responsible for this action is the alpha-smooth muscle actin (alpha-SMA)-expressing myofibroblast. Abnormal persistence of the myofibroblast is a hallmark of fibrotic diseases. Proteins such as transforming growth factor (TGF)beta, endothelin-1, angiotensin II (Ang II), connective tissue growth factor (CCN2/CTGF), and platelet-derived growth factor (PDGF) appear to act in a network that contributes to myofibroblast differentiation and persistence. Drugs targeting these proteins are currently under consideration as antifibrotic treatments. This review summarizes recent observations concerning the contribution of TGFbeta, endothelin-1, Ang II, CCN2, and PDGF and to fibroblast activation in tissue repair and fibrosis and the potential utility of agents blocking these proteins in affecting the outcome of cardiac fibrosis.
纤维化是最大的疾病群体之一，目前尚无治疗方法，但据信它是由于持续的组织修复程序而发生的。在结缔组织修复过程中，“激活”的成纤维细胞迁移到伤口区域，在那里它们合成和重塑新创建的细胞外基质。负责这种作用的特殊类型的成纤维细胞是表达α-平滑肌肌动蛋白（α-SMA）的肌成纤维细胞。肌成纤维细胞的异常持续存在是纤维化疾病的标志。转化生长因子 (TGF)β、内皮素-1、血管紧张素 II (Ang II)、结缔组织生长因子 (CCN2/CTGF) 和血小板衍生生长因子 (PDGF) 等蛋白似乎在一个网络中发挥作用，有助于肌成纤维细胞分化和持续存在。针对这些蛋白的药物目前正在考虑作为抗纤维化治疗。本综述总结了最近关于 TGFβ、内皮素-1、Ang II、CCN2 和 PDGF 以及这些蛋白在组织修复和纤维化中对成纤维细胞激活的贡献的观察结果，以及阻断这些蛋白的药物在影响心脏纤维化结果方面的潜在用途。
