Wu Kai, Ji Jia, Pan Jingying, Zhu Miaojin, Zhang Jiale, Sun Ting, Lv Dan, Wei Mudan, Wang Minghai, Yao Hangping
State Key Laboratory for Diagnosis, Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.
Jinan Microecological Biomedicine Shandong Laboratory, Jinan, 250000, China.
Cell Commun Signal. 2025 Aug 28;23(1):385. doi: 10.1186/s12964-025-02407-5.
The liver is a crucial organ in the human body and is responsible for various functions, including digestion, detoxification, metabolism, and immune response. Proper hepatic function is vital for maintaining systemic homeostasis, and dysregulation of liver signaling pathways contributes to various diseases. Recepteur d'Origine Nantais (RON) is a transmembrane receptor tyrosine kinase that is activated by macrophage-stimulating protein (MSP) and coordinates cell fate decisions through the activation of downstream signaling cascades. As the predominant source of MSP in humans, the liver establishes a liver-specific MSP‒RON autocrine‒paracrine signaling axis that contributes to hepatic regeneration, metabolism, and immune functions. Extensive research has demonstrated that MSP-RON signaling is involved in steatotic liver diseases, hepatitis, cirrhosis, cholestatic liver disease, and liver cancer, highlighting the importance of RON in the development of liver diseases. This review demonstrates the role of the MSP-RON pathway both in maintaining liver homeostasis and in driving disease onset and progression while exploring its signaling mechanisms and therapeutic potential for liver disorders.
肝脏是人体中的一个关键器官，负责多种功能，包括消化、解毒、代谢和免疫反应。正常的肝功能对于维持全身稳态至关重要，而肝脏信号通路的失调会导致各种疾病。南特起源受体（RON）是一种跨膜受体酪氨酸激酶，可被巨噬细胞刺激蛋白（MSP）激活，并通过激活下游信号级联反应来协调细胞命运决定。作为人类MSP的主要来源，肝脏建立了一个肝脏特异性的MSP-RON自分泌-旁分泌信号轴，该信号轴有助于肝脏再生、代谢和免疫功能。大量研究表明，MSP-RON信号传导参与脂肪性肝病、肝炎、肝硬化、胆汁淤积性肝病和肝癌，突出了RON在肝脏疾病发生发展中的重要性。本综述阐述了MSP-RON通路在维持肝脏稳态以及推动疾病发生和进展中的作用，同时探讨了其信号传导机制和对肝脏疾病的治疗潜力。
