Iredale John P, Thompson Alexandra, Henderson Neil C
MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
Biochim Biophys Acta. 2013 Jul;1832(7):876-83. doi: 10.1016/j.bbadis.2012.11.002. Epub 2012 Nov 10.
Fibrosis is a highly conserved wound healing response and represents the final common pathway of virtually all chronic inflammatory injuries. Over the past 3 decades detailed analysis of hepatic extracellular matrix synthesis and degradation using approaches incorporating human disease, experimental animal models and cell culture have highlighted the extraordinarily dynamic nature of tissue repair and remodelling in this solid organ. Furthermore emerging studies of fibrosis in other organs demonstrate that basic common mechanisms exist, suggesting that bidirectionality of the fibrotic process may not solely be the preserve of the liver. In this review we will examine the cellular and molecular mechanisms that govern extracellular matrix degradation and fibrosis resolution, and highlight how manipulation of these processes may result in the development of effective anti-fibrotic therapies. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease.
纤维化是一种高度保守的伤口愈合反应,几乎代表了所有慢性炎症损伤的最终共同途径。在过去30年里,通过结合人类疾病、实验动物模型和细胞培养的方法,对肝细胞外基质的合成和降解进行了详细分析,突出了这个实体器官中组织修复和重塑的异常动态性质。此外,对其他器官纤维化的新研究表明,存在基本的共同机制,这表明纤维化过程的双向性可能并非肝脏所特有。在这篇综述中,我们将研究控制细胞外基质降解和纤维化消退的细胞和分子机制,并强调对这些过程的操控如何可能促成有效的抗纤维化疗法的开发。本文是名为《纤维化:基础研究向人类疾病的转化》的特刊的一部分。