Connective tissue growth factor: a new and important player in the pathogenesis of fibrosis.
Connective tissue growth factor: a new and important player in the pathogenesis of fibrosis.
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DOI：
10.1007/s11926-002-0009-x
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发表时间：
2002-04-01
影响因子：
5
通讯作者：
Abraham, David J
中科院分区：
文献类型：
--
作者：
Leask, Andrew;Holmes, Alan;Abraham, David J
结缔组织纤维化是几乎所有形式的慢性组织损伤的最终共同致病过程。无论是由血管功能障碍、炎症、代谢损伤、创伤还是环境因素引起的，纤维化过程一旦启动，就会导致正常组织结构逐渐被纤维化病变所取代，最终导致器官损害和衰竭。纤维化可以认为是正常组织修复机制的失调，导致严重的组织瘢痕形成。纤维化似乎是相关过程的结果，包括常驻成纤维细胞类型的增殖，细胞外基质成分的产生和沉积增加，以及成纤维细胞向肌成纤维细胞表型的细胞转变。虽然转化生长因子- β (TGF β)一直被认为是结缔组织形成和维持的关键生长因子，也是许多进行性纤维化疾病的主要驱动因素，但结缔组织生长因子（CTGF）在纤维化中的作用近年来受到关注。CTGF在间充质源性细胞中被TGF β选择性、快速诱导。CTGF在许多纤维化疾病中表达升高。此外，越来越多来自体内和体外组织重塑和纤维化模型的证据表明，在结缔组织的维持和修复以及纤维化疾病环境中，CTGF可能是TGF β促纤维化活性的下游效应分子。
Connective tissue fibrosis is the final common pathogenic process for almost all forms of chronic tissue injury. Whether caused by vascular dysfunction, inflammation, metabolic injury, trauma, or environmental agents, once initiated the fibrogenic process results in the progressive replacement of the normal tissue architecture with fibrotic lesions that eventually lead to organ compromise and failure. Fibrosis can be considered as a dysregulation in the normal tissue repair mechanism, resulting in severe tissue scarring. Fibrosis appears to be a consequence of linked processes, including the proliferation of resident fibroblast cell types, the increased production and deposition of extracellular matrix components, and the transition of fibroblasts into cells exhibiting a myofibroblast phenotype. Although transforming growth factor-beta (TGF beta) has long been regarded as a pivotal growth factor in the formation and maintenance of connective tissues and as a major driving influence in many progressive fibrotic diseases, attention has focused recently on the role of connective tissue growth factor (CTGF) in fibrosis. CTGF is selectively and rapidly induced in mesenchymally derived cells by the action of TGF beta. CTGF expression is increased in many fibrosing diseases. In addition, increasing evidence from in vivo and in vitro models of tissue remodeling and fibrosis suggest that CTGF may represent a downstream effector molecule of the profibrotic activities of TGF beta in the maintenance and repair of connective tissues and within fibrotic disease settings.