Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Fitzgerald Building, Room 234, 150 College Street, Toronto, ON M5S 3E2, Canada.
Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Fitzgerald Building, Room 234, 150 College Street, Toronto, ON M5S 3E2, Canada.
Matrix Biol. 2018 Oct;71-72:205-224. doi: 10.1016/j.matbio.2018.02.020. Epub 2018 Feb 27.
Organ fibrosis is characterized by the accumulation of disorganized and stiff extracellular matrix (ECM) and represents the final stage of several life-threatening diseases. The progressive replacement of normal tissue by fibrotic ECM impedes organ functionality to the point of failure. Fibrosis affects millions of people worldwide with no effective cure for various reasons: (a) Due to the lack of clinical biomarkers and non-invasive detection methods fibrosis is often diagnosed too late, when organs are already destroyed beyond repair. (b) Fibrosis can be understood as dysregulated tissue repair that evolved robust programs to be able to respond to various injury scenarios. The redundant nature of these programs often evades linear therapeutic strategies. (c) Fibrosis perpetuates itself by establishing conditions that activate normal into fibrogenic cells which, in turn, create a pro-fibrotic environment. ECM takes center stage in the process of fibrosis as a defining feature and thus potential diagnostic biomarker. The ECM is also a main promoter of the disease process by providing lasting physicochemical pro-fibrotic cues to residing and recruiting cells. Effective anti-fibrotic therapies will need to take the lasting (mis-) instructive character of scar ECM into account. To restore organ functionality, it will be important to (re)turn fibrotic scar into functional ECM, for instance by dissolving fibrotic ECM and delivering cells with regenerative potential.
器官纤维化的特征是细胞外基质（ECM）的无序和僵硬积累，代表了几种危及生命疾病的终末阶段。纤维化 ECM 的渐进性替代正常组织会阻碍器官功能，直至衰竭。由于多种原因，纤维化影响着全球数百万人，目前尚无有效的治疗方法：（a）由于缺乏临床生物标志物和非侵入性检测方法，纤维化通常在器官已经受损无法修复时被诊断出来，为时已晚。（b）纤维化可以被理解为失调的组织修复，它进化出了强大的程序来应对各种损伤情况。这些程序的冗余性质常常规避了线性治疗策略。（c）纤维化通过创造条件使正常细胞转化为成纤维细胞来维持自身，而这些成纤维细胞反过来又创造了一个促纤维化的环境。ECM 在纤维化过程中处于中心地位，既是特征，也是潜在的诊断生物标志物。ECM 通过为驻留和募集的细胞提供持久的物理化学促纤维化线索，也是疾病过程的主要促进因素。有效的抗纤维化治疗需要考虑到疤痕 ECM 的持久（错误）指导特征。为了恢复器官功能，将纤维化疤痕（re)转化为功能性 ECM 将非常重要，例如通过溶解纤维化 ECM 并输送具有再生潜力的细胞。
