Mercer Paul F, Chambers Rachel C
Centre for Inflammation and Tissue Repair, University College London, Rayne Institute, 5 University St., London WC1E 6JF, UK.
Biochim Biophys Acta. 2013 Jul;1832(7):1018-27. doi: 10.1016/j.bbadis.2012.12.013. Epub 2013 Jan 5.
Following tissue injury, a complex and coordinated wound healing response comprising coagulation, inflammation, fibroproliferation and tissue remodelling has evolved to nullify the impact of the original insult and reinstate the normal physiological function of the affected organ. Tissue fibrosis is thought to result from a dysregulated wound healing response as a result of continual local injury or impaired control mechanisms. Although the initial insult is highly variable for different organs, in most cases, uncontrolled or sustained activation of mesenchymal cells into highly synthetic myofibroblasts leads to the excessive deposition of extracellular matrix proteins and eventually loss of tissue function. Coagulation was originally thought to be an acute and transient response to tissue injury, responsible primarily for promoting haemostasis by initiating the formation of fibrin plugs to enmesh activated platelets within the walls of damaged blood vessels. However, the last 20years has seen a major re-evaluation of the role of the coagulation cascade following tissue injury and there is now mounting evidence that coagulation plays a critical role in orchestrating subsequent inflammatory and fibroproliferative responses during normal wound healing, as well as in a range of pathological contexts across all major organ systems. This review summarises our current understanding of the role of coagulation and coagulation initiated signalling in the response to tissue injury, as well as the contribution of uncontrolled coagulation to fibrosis of the lung, liver, kidney and heart. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease.
组织损伤后，机体进化出了一个复杂且协调的伤口愈合反应，包括凝血、炎症、纤维增殖和组织重塑，以消除原始损伤的影响并恢复受影响器官的正常生理功能。组织纤维化被认为是由于持续的局部损伤或控制机制受损导致伤口愈合反应失调所致。尽管不同器官的初始损伤差异很大，但在大多数情况下，间充质细胞不受控制或持续激活转化为高合成性的肌成纤维细胞会导致细胞外基质蛋白过度沉积，最终导致组织功能丧失。凝血最初被认为是对组织损伤的一种急性和短暂反应，主要负责通过启动纤维蛋白凝块的形成来促进止血，从而将活化的血小板困在受损血管壁内。然而，在过去的20年里，人们对组织损伤后凝血级联反应的作用进行了重大重新评估，现在有越来越多的证据表明，凝血在正常伤口愈合过程中协调随后的炎症和纤维增殖反应以及在所有主要器官系统的一系列病理情况下都起着关键作用。本综述总结了我们目前对凝血及凝血引发的信号传导在组织损伤反应中的作用的理解，以及不受控制的凝血对肺、肝、肾和心脏纤维化的影响。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。
