Greenhalgh S N, Conroy K P, Henderson N C
From the MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
From the MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
QJM. 2015 Jan;108(1):3-7. doi: 10.1093/qjmed/hcu067. Epub 2014 Mar 22.
Fibrosis, with resultant loss of organ function, is the endpoint of many diseases. Despite this, no effective anti-fibrotic therapies exist. The myofibroblast is the key cell driving fibrosis but its origins remain controversial. A growing body of work provides strong evidence that the pericyte, a perivascular cell present throughout the microvasculature, is a major myofibroblast precursor in multiple tissues. This review summarizes the principle experimental and clinical evidence underpinning this conclusion and outlines strategies for targeting pericyte transdifferentiation during fibrogenesis. Successful targeting of pro-fibrogenic pericytes has the potential to halt or even reverse fibrosis and thus reduce the enormous worldwide healthcare burden that currently exists as a result of fibrotic disease.
纤维化以及随之而来的器官功能丧失,是许多疾病的终点。尽管如此,目前尚无有效的抗纤维化疗法。肌成纤维细胞是驱动纤维化的关键细胞,但其起源仍存在争议。越来越多的研究工作提供了强有力的证据,表明周细胞(一种存在于整个微脉管系统的血管周围细胞)是多种组织中主要的肌成纤维细胞前体。本综述总结了支持这一结论的主要实验和临床证据,并概述了在纤维化形成过程中靶向周细胞转分化的策略。成功靶向促纤维化周细胞有可能阻止甚至逆转纤维化,从而减轻目前因纤维化疾病而在全球造成的巨大医疗负担。