Abraham D
Research Department of Inflammation, Division of Medicine, Centre for Rheumatology and Connective Tissue Diseases, Royal Free and University College Medical School, University College London, Royal Free Campus, London, UK.
Rheumatology (Oxford). 2008 Oct;47 Suppl 5:v8-9. doi: 10.1093/rheumatology/ken278.
SSc is characterized by enhanced extracellular matrix (ECM) production resulting in excessive scarring and replacement fibrosis affecting the interstitial and vascular compartments of multiple organs. Although the precise molecular mechanisms driving fibrosis remain elusive, TGF-beta and connective tissue growth factor (CTGF), are considered key mediators. CTGF is over-expressed in lesional tissue and enhanced levels in the circulation are an indicator of disease extent and severity. Rapidly induced by TGF-beta and ET-1, CTGF activates several signal transduction pathways via surface receptors that modulate the functional activities of fibroblasts, endothelial and smooth muscle cells. In vivo, over-expression of CTGF causes ECM accumulation and promotes tissue fibrosis. In animal models of SSc, neutralization of CTGF with antibody blockade or siRNA, suppresses fibrogenesis. This article examines the role of CTGF as an integrator of extracellular signals, fibrotic biomarker and discusses the potential value of CTGF antagonism as a therapeutic strategy in SSc.
系统性硬化症（SSc）的特征是细胞外基质（ECM）生成增加，导致过度瘢痕形成和替代性纤维化，影响多个器官的间质和血管腔隙。尽管驱动纤维化的确切分子机制仍不清楚，但转化生长因子-β（TGF-β）和结缔组织生长因子（CTGF）被认为是关键介质。CTGF在病变组织中过度表达，循环中水平升高是疾病范围和严重程度的指标。CTGF由TGF-β和内皮素-1（ET-1）快速诱导，通过表面受体激活多种信号转导途径，调节成纤维细胞、内皮细胞和平滑肌细胞的功能活性。在体内，CTGF的过度表达会导致ECM积累并促进组织纤维化。在SSc动物模型中，用抗体阻断或小干扰RNA（siRNA）中和CTGF可抑制纤维化形成。本文探讨了CTGF作为细胞外信号整合器、纤维化生物标志物的作用，并讨论了CTGF拮抗作用作为SSc治疗策略的潜在价值。
