纤维化的特征是由于伤口和结缔组织修复反应失调导致细胞外基质过度沉积。多个器官会发生纤维化,包括肝脏、肾脏、心脏和肺。肝硬化、特发性肺纤维化和囊性纤维化等纤维化造成了巨大的疾病负担。由转化生长因子、血小板衍生生长因子和成纤维细胞生长因子等多种信号介导的肌成纤维细胞持续异常激活已被认为是纤维化发生和进展的重大事件。尽管驱动器官特异性纤维化的机制尚未完全阐明,但针对这些已识别异常信号的药物已在临床试验中取得了有效的抗纤维化功效。在这篇评论中,我们简要介绍几种纤维化疾病的病因和流行病学,包括肝纤维化、肾纤维化、心脏纤维化和肺纤维化。然后,我们总结了异常细胞(上皮细胞、内皮细胞、免疫细胞和成纤维细胞)及其在纤维化中的相互作用。此外,我们还关注调节肌成纤维细胞活化、细胞外基质交联、代谢和纤维化炎症的异常信号通路和治疗靶点。最后,我们根据其靶点和临床试验讨论抗纤维化药物。本综述为进一步研究纤维化机制、药物开发和临床试验提供参考。我们总结了异常细胞(上皮细胞、内皮细胞、免疫细胞和成纤维细胞)及其在纤维化中的相互作用。此外,我们还关注调节肌成纤维细胞活化、细胞外基质交联、代谢和纤维化炎症的异常信号通路和治疗靶点。最后,我们根据其靶点和临床试验讨论抗纤维化药物。本综述为进一步研究纤维化机制、药物开发和临床试验提供参考。我们总结了异常细胞(上皮细胞、内皮细胞、免疫细胞和成纤维细胞)及其在纤维化中的相互作用。此外,我们还关注调节肌成纤维细胞活化、细胞外基质交联、代谢和纤维化炎症的异常信号通路和治疗靶点。最后,我们根据其靶点和临床试验讨论抗纤维化药物。本综述为进一步研究纤维化机制、药物开发和临床试验提供参考。和炎症纤维化。最后,我们根据其靶点和临床试验讨论抗纤维化药物。本综述为进一步研究纤维化机制、药物开发和临床试验提供参考。和炎症纤维化。最后,我们根据其靶点和临床试验讨论抗纤维化药物。本综述为进一步研究纤维化机制、药物开发和临床试验提供参考。
"点击查看英文标题和摘要"
Targeting fibrosis, mechanisms and cilinical trials
Fibrosis is characterized by the excessive extracellular matrix deposition due to dysregulated wound and connective tissue repair response. Multiple organs can develop fibrosis, including the liver, kidney, heart, and lung. Fibrosis such as liver cirrhosis, idiopathic pulmonary fibrosis, and cystic fibrosis caused substantial disease burden. Persistent abnormal activation of myofibroblasts mediated by various signals, such as transforming growth factor, platelet-derived growth factor, and fibroblast growh factor, has been recongized as a major event in the occurrence and progression of fibrosis. Although the mechanisms driving organ-specific fibrosis have not been fully elucidated, drugs targeting these identified aberrant signals have achieved potent anti-fibrotic efficacy in clinical trials. In this review, we briefly introduce the aetiology and epidemiology of several fibrosis diseases, including liver fibrosis, kidney fibrosis, cardiac fibrosis, and pulmonary fibrosis. Then, we summarise the abnormal cells (epithelial cells, endothelial cells, immune cells, and fibroblasts) and their interactions in fibrosis. In addition, we also focus on the aberrant signaling pathways and therapeutic targets that regulate myofibroblast activation, extracellular matrix cross-linking, metabolism, and inflammation in fibrosis. Finally, we discuss the anti-fibrotic drugs based on their targets and clinical trials. This review provides reference for further research on fibrosis mechanism, drug development, and clinical trials.