School of Medicine, Shanghai Jiao Tong University, 227 Chongqing South Road, Shanghai 200011, China.
Center of Craniofacial Orthodontics, Department of Oral and Cranio-maxillofacial Science, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Disease, Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, China.
Pharmacol Res. 2024 Oct;208:107348. doi: 10.1016/j.phrs.2024.107348. Epub 2024 Aug 10.
Fibrosis refers to the progressive tissue lesion process characterized by excessive secretion and deposition of extracellular matrix (ECM). Abnormal fibrous tissue deposition distorts tissue architecture and leads to the progressive loss of organ function. Notably, fibrosis is one of the primary pathological appearances of many end stage illnesses, and is considered as a lethal threat to human health, especially in the elderly with ageing-related diseases. CX3C ligand 1 (CX3CL1) is the only member of chemokine CX3C and binds specifically to CX3C receptor 1 (CX3CR1). Different from other chemokines, CX3CL1 possesses both chemotactic and adhesive activity. CX3CL1/CX3CR1 axis involves in various physiological and pathological processes, and exerts a critical role in cells from the immune system, vascular system, and nervous system etc. Notably, increasing evidence has demonstrated that CX3CL1/CX3CR1 signaling pathway is closely related to the pathological process of fibrosis in multiple tissue and organs. We reviewed the crucial role of CX3CL1/CX3CR1 axis in fibrosis and ageing and systematically summarized the underlying mechanism, which offers prospective strategies of targeting CX3C for the therapy of fibrosis and ageing-related diseases.
纤维化是指以细胞外基质（ECM）过度分泌和沉积为特征的进行性组织损伤过程。异常纤维组织的沉积破坏了组织的结构，并导致器官功能的进行性丧失。值得注意的是，纤维化是许多终末期疾病的主要病理表现之一，被认为是对人类健康的致命威胁，尤其是在与年龄相关的疾病的老年人中。趋化因子 CX3C 配体 1（CX3CL1）是趋化因子 CX3C 家族中唯一的成员，特异性结合趋化因子 CX3C 受体 1（CX3CR1）。与其他趋化因子不同，CX3CL1 具有趋化和黏附活性。CX3CL1/CX3CR1 轴参与各种生理和病理过程，并在免疫系统、血管系统和神经系统等细胞中发挥关键作用。值得注意的是，越来越多的证据表明，CX3CL1/CX3CR1 信号通路与多种组织和器官的纤维化病理过程密切相关。我们综述了 CX3CL1/CX3CR1 轴在纤维化和衰老中的关键作用，并系统总结了其潜在机制，为靶向 CX3C 治疗纤维化和衰老相关疾病提供了有前景的策略。
