Campana Lara, Iredale John P
Centre for Inflammation Research and Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Senate House, University of Bristol, Bristol, United Kingdom.
Semin Liver Dis. 2017 Feb;37(1):1-10. doi: 10.1055/s-0036-1597816. Epub 2017 Feb 15.
Liver fibrosis is the final common pathway of chronic or iterative liver damage. Advanced chronic fibrosis is described as cirrhosis with a loss of architecture and attendant functional failure and the development of life-threatening complications. However, compelling evidence from rodent models and human studies indicates that if the injury is removed liver fibrosis is reversible. Hepatocytes, activated hepatic stellate cells, endothelial and immune cells, particularly macrophages, cooperate in the establishment and resolution of liver fibrosis. Here the authors provide a short overview of the mechanisms regulating the profibrotic and proresolution response, with the aim of highlighting potential new therapeutic targets. Liver disease is a major unmet medical need; currently, the sole approaches are the withdrawal of the injurious stimulus and liver transplantation. The authors conclude with a brief review of the feasibility of macrophage-based cell therapy for liver fibrosis.
肝纤维化是慢性或反复性肝损伤的最终共同途径。晚期慢性纤维化被描述为伴有结构丧失、随之而来的功能衰竭以及危及生命并发症发生的肝硬化。然而,来自啮齿动物模型和人体研究的确凿证据表明,如果去除损伤因素,肝纤维化是可逆的。肝细胞、活化的肝星状细胞、内皮细胞和免疫细胞,尤其是巨噬细胞,在肝纤维化的形成和消退过程中相互协作。在此,作者简要概述了调节促纤维化和促消退反应的机制,旨在突出潜在的新治疗靶点。肝脏疾病是一项尚未满足的重大医疗需求;目前,唯一的治疗方法是去除损伤性刺激和肝移植。作者最后简要回顾了基于巨噬细胞的细胞疗法治疗肝纤维化的可行性。