Shriners Hospital for Children, Division of Surgical Research, McGill University, 1529 Cedar Avenue, Montreal, QC H3G1A6, Canada.
Pulmonary and Critical Care Unit and Centre for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA.
Nat Rev Rheumatol. 2014 Jul;10(7):390-402. doi: 10.1038/nrrheum.2014.53. Epub 2014 Apr 22.
Fibrosis is a pathological process characterized by excessive accumulation of connective tissue components in an organ or tissue. Fibrosis is produced by deregulated wound healing in response to chronic tissue injury or chronic inflammation, the hallmarks of rheumatic diseases. Progressive fibrosis, which distorts tissue architecture and results in progressive loss of organ function, is now recognized to be one of the major causes of morbidity and mortality in individuals with one of the most lethal rheumatic disease, systemic sclerosis (SSc). In this Review, we discuss the pathological role of fibrosis in SSc. We discuss the involvement of endothelium and pericyte activation, aberrant immune responses, endoplasmic reticulum stress and chronic tissue injury in the initiation of fibrosis in SSc. We then discuss fibroblast activation and myofibroblast differentiation that occurs in response to these initiating processes and is responsible for excessive accumulation of extracellular matrix. Finally, we discuss the chemical and mechanical signals that drive fibroblast activation and myofibroblast differentiation, which could serve as targets for new therapies for fibrosis in SSc.
纤维化是一种病理过程，其特征是器官或组织中结缔组织成分的过度积累。纤维化是由于慢性组织损伤或慢性炎症导致的失调性伤口愈合引起的，这是风湿性疾病的标志。进行性纤维化会破坏组织架构并导致器官功能逐渐丧失，这已被认为是最致命的风湿性疾病之一——全身性硬皮病（systemic sclerosis，SSc）患者发病率和死亡率的主要原因之一。在这篇综述中，我们讨论了纤维化在 SSc 中的病理作用。我们讨论了内皮细胞和周细胞激活、异常免疫反应、内质网应激和慢性组织损伤在 SSc 纤维化起始中的作用。然后，我们讨论了成纤维细胞的激活和肌成纤维细胞的分化，这些反应是对这些起始过程的反应，是细胞外基质过度积累的原因。最后，我们讨论了驱动成纤维细胞激活和肌成纤维细胞分化的化学和机械信号，这些信号可能成为 SSc 纤维化新疗法的靶点。
