DAMP信号网络：从受体到多种病理生理功能

DAMP signaling networks: from receptors to diverse pathophysiological functions.

作者信息

Chen Ruochan, Zou Ju, Zhong Xiao, Liu Jiao, Kang Rui, Tang Daolin

机构信息

Department of Infectious Disease, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570311, China; Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Department of Infectious Disease, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China.

Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Department of Infectious Disease, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders (Xiangya), Changsha, Hunan, China.

出版信息

J Adv Res. 2025 Jul 31. doi: 10.1016/j.jare.2025.07.047.

DOI:10.1016/j.jare.2025.07.047

PMID:40752681

Abstract

BACKGROUND

Damage-associated molecular patterns (DAMPs) are endogenous molecules released or exposed during cellular stress, injury, or death. Initially characterized as danger signals that alert the immune system, DAMPs are now recognized as pivotal regulators of innate and adaptive immunity through receptor-mediated signaling mechanisms.

AIM OF REVIEW

This review aims to elucidate the diverse receptors and intracellular signaling pathways activated by DAMPs and to explore their multifaceted roles in immune modulation, tissue repair, and disease pathogenesis.

KEY SCIENTIFIC CONCEPTS OF REVIEW

DAMP receptors are broadly divided into pattern recognition receptors (PRRs) such as TLRs, NLRs, and RLRs, and non-PRR receptors such as GPCRs, AGER/RAGE, and ion channels. Activation of these receptors initiates downstream signaling cascades including NF-κB, MAPK, and cGAS-STING pathways. DAMP signaling orchestrates a broad range of immunological and cellular processes, including the activation of immune responses, modulation of cell proliferation and migration, promotion of fibrosis and angiogenesis, and the induction of regulated cell death pathways. Dysregulation of DAMP signaling contributes to the pathogenesis of infectious diseases, autoimmune disorders, and cancer, highlighting its potential as a therapeutic target.

摘要

背景

损伤相关分子模式（DAMPs）是细胞应激、损伤或死亡期间释放或暴露的内源性分子。DAMPs最初被表征为警示免疫系统的危险信号，现在通过受体介导的信号机制被认为是先天性和适应性免疫的关键调节因子。

综述目的

本综述旨在阐明由DAMPs激活的多种受体和细胞内信号通路，并探讨它们在免疫调节、组织修复和疾病发病机制中的多方面作用。

综述的关键科学概念

DAMP受体大致分为模式识别受体（PRRs），如Toll样受体（TLRs）、NOD样受体（NLRs）和视黄酸诱导基因I样受体（RLRs），以及非PRR受体，如G蛋白偶联受体（GPCRs）、晚期糖基化终末产物受体（AGER/RAGE）和离子通道。这些受体的激活启动下游信号级联反应，包括核因子κB（NF-κB）、丝裂原活化蛋白激酶（MAPK）和环鸟苷酸-腺苷酸合成酶-干扰素基因刺激蛋白（cGAS-STING）途径。DAMP信号协调广泛的免疫和细胞过程，包括免疫反应的激活、细胞增殖和迁移的调节、纤维化和血管生成的促进以及程序性细胞死亡途径的诱导。DAMP信号失调导致传染病、自身免疫性疾病和癌症的发病机制，突出了其作为治疗靶点的潜力。