Renal Section, Department of Medicine, Imperial College London, London, UK.
Int J Exp Pathol. 2013 Feb;94(1):1-16. doi: 10.1111/j.1365-2613.2012.00845.x. Epub 2012 Oct 30.
Connective tissue growth factor (CTGF, CCN2) is a member of the CCN family of matricellular proteins. It interacts with many other proteins, including plasma membrane proteins, modulating cell function. It is expressed at low levels in normal adult kidney cells but is increased in kidney diseases, playing important roles in inflammation and in the development of glomerular and interstitial fibrosis in chronic disease. This review reports the evidence for its expression in human and animal models of chronic kidney disease and summarizes data showing that anti-CTGF therapy can successfully attenuate fibrotic changes in several such models, suggesting that therapies targeting CTGF and events downstream of it in renal cells may be useful for the treatment of human kidney fibrosis. Connective tissue growth factor stimulates the development of fibrosis in the kidney in many ways including activating cells to increase extracellular matrix synthesis, inducing cell cycle arrest and hypertrophy, and prolonging survival of activated cells. The relationship between CTGF and the pro-fibrotic factor TGFβ is examined and mechanisms by which CTGF promotes signalling by the latter are discussed. No specific cellular receptors for CTGF have been discovered but it interacts with and activates several plasma membrane proteins including low-density lipoprotein receptor-related protein (LRP)-1, LRP-6, tropomyosin-related kinase A, integrins and heparan sulphate proteoglycans. Intracellular signalling and downstream events triggered by such interactions are reviewed. Finally, the relationships between CTGF and several anti-fibrotic factors, such as bone morphogenetic factor-4 (BMP4), BMP7, hepatocyte growth factor, CCN3 and Oncostatin M, are discussed. These may determine whether injured tissue heals or progresses to fibrosis.
结缔组织生长因子（CTGF，CCN2）是细胞外基质蛋白细胞反应因子（CCN）家族的一员。它与许多其他蛋白质相互作用，包括质膜蛋白，调节细胞功能。在正常成年肾脏细胞中低表达，但在肾脏疾病中增加，在炎症和慢性疾病肾小球和间质纤维化的发展中发挥重要作用。这篇综述报告了其在人类和动物慢性肾脏病模型中的表达证据，并总结了数据表明，抗 CTGF 治疗可以成功减轻几种模型中的纤维化变化，这表明针对 CTGF 和肾脏细胞中其下游事件的治疗可能对人类肾脏纤维化的治疗有用。结缔组织生长因子通过多种方式刺激肾脏纤维化的发展，包括激活细胞增加细胞外基质合成、诱导细胞周期停滞和肥大，以及延长激活细胞的存活。检查了 CTGF 与促纤维化因子 TGFβ 之间的关系，并讨论了 CTGF 促进后者信号转导的机制。尚未发现 CTGF 的特定细胞受体，但它与几种质膜蛋白相互作用并激活它们，包括低密度脂蛋白受体相关蛋白（LRP）-1、LRP-6、原肌球蛋白相关激酶 A、整合素和硫酸乙酰肝素蛋白聚糖。综述了这些相互作用引发的细胞内信号转导和下游事件。最后，讨论了 CTGF 与几种抗纤维化因子之间的关系，如骨形态发生蛋白 4（BMP4）、BMP7、肝细胞生长因子、CCN3 和 Oncostatin M，这些因子可能决定受损组织是愈合还是进展为纤维化。
