Chen Xiangqi, Zhang Jinhang, Guo Ling, Wu Chuan, Zhou Jingyue, Xu Mingzhu, Mo Li, Li Yanping, He Jinhan
Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, West China Hospital, Sichuan University, Chengdu, China.
National Engineering Technology Research Center for Miao Medicine, Guizhou Engineering Technology Research Center for Processing and Preparation of Traditional Chinese Medicine and Ethnic Medicine, College of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine, Guiyang, China.
Signal Transduct Target Ther. 2026 Mar 6;11(1):82. doi: 10.1038/s41392-025-02532-0.
Fibrosis is a maladaptive pathophysiological process characterized by excessive deposition of extracellular matrix resulting from dysregulated tissue repair responses. Fibrosis can affect nearly all organ systems, such as the lung, heart, liver, and kidney. Persistent fibrotic remodeling leads to architectural distortion, loss of function, organ failure, and ultimately increased mortality. These devastating outcomes highlight the urgent need for effective antifibrotic therapies. Advances in multiomics technologies have revealed that fibrosis represents a dynamic alteration spanning the molecular, cellular, microenvironmental, and organ levels. Despite impressive progress in our understanding of fibrogenesis over recent years, a substantial translational gap remains between identifying potential antifibrotic targets and translating this theoretical knowledge into effective human therapies. To further understand pathogenesis and facilitate the development of novel antifibrotic drugs, this review summarizes crucial milestones in fibrosis research, elaborates on organ-specific pathogenic mechanisms, and details the phenotypic and functional changes in critical cellular players, including parenchymal cells, fibroblasts, endothelial cells, and immune cells. Furthermore, this review outlines the key signaling pathways implicated in the pathogenesis of fibrosis, provides a comprehensive overview of relevant clinical trials, and discusses promising future research directions, including cross-organ multiomics integration, chimeric antigen receptor therapy, and artificial intelligence technology applications.
纤维化是一种适应性不良的病理生理过程，其特征是组织修复反应失调导致细胞外基质过度沉积。纤维化可影响几乎所有器官系统，如肺、心脏、肝脏和肾脏。持续性纤维化重塑会导致结构扭曲、功能丧失、器官衰竭，并最终增加死亡率。这些灾难性后果凸显了对有效抗纤维化疗法的迫切需求。多组学技术的进展表明，纤维化代表了一个跨越分子、细胞、微环境和器官水平的动态变化。尽管近年来我们对纤维化发生机制的理解取得了令人瞩目的进展，但在确定潜在的抗纤维化靶点并将这一理论知识转化为有效的人类治疗方法之间，仍存在巨大的转化差距。为了进一步了解发病机制并促进新型抗纤维化药物的开发，本综述总结了纤维化研究中的关键里程碑，阐述了器官特异性致病机制，并详细介绍了关键细胞参与者（包括实质细胞、成纤维细胞、内皮细胞和免疫细胞）的表型和功能变化。此外，本综述概述了与纤维化发病机制相关的关键信号通路，全面综述了相关临床试验，并讨论了有前景的未来研究方向，包括跨器官多组学整合、嵌合抗原受体疗法和人工智能技术应用。
