Aziz Monowar, Chaudry Irshad H, Wang Ping
Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA.
Departments of Surgery and Molecular Medicine, Zucker School of Medicine, Manhasset, NY 11030, USA.
Int J Mol Sci. 2025 Apr 9;26(8):3524. doi: 10.3390/ijms26083524.
Extracellular cold-inducible RNA-binding protein (eCIRP) is a critical damage-associated molecular pattern (DAMP) that drives inflammation and tissue injury in hemorrhagic and septic shock, and has emerged as a promising therapeutic target. Since then, extensive research using preclinical models of diseases and patient materials has explored eCIRP's role in driving inflammatory responses and its potential as a biomarker. The main objective of this comprehensive review is to provide a detailed overview of eCIRP, covering its discovery, role in disease pathophysiology, mechanisms of release and action, potential as a biomarker, and therapeutic strategies targeting eCIRP in preclinical models of inflammatory and ischemic diseases. We examine the molecular, cellular, and immunological mechanisms through which eCIRP contributes to disease progression, and explore both well-established and emerging areas of research. Furthermore, we discuss potential therapeutic strategies targeting eCIRP across a broad spectrum of inflammatory conditions, including shock, ischemia-reperfusion injury, neurodegenerative diseases, and radiation injury.
细胞外冷诱导RNA结合蛋白（eCIRP）是一种关键的损伤相关分子模式（DAMP），在出血性休克和脓毒性休克中驱动炎症和组织损伤，并已成为一个有前景的治疗靶点。从那时起，利用疾病的临床前模型和患者材料进行的广泛研究探索了eCIRP在驱动炎症反应中的作用及其作为生物标志物的潜力。这篇综述的主要目的是对eCIRP进行详细概述，涵盖其发现、在疾病病理生理学中的作用、释放和作用机制、作为生物标志物的潜力以及在炎症和缺血性疾病临床前模型中针对eCIRP的治疗策略。我们研究了eCIRP促进疾病进展的分子、细胞和免疫机制，并探索了已确立和新兴的研究领域。此外，我们讨论了针对广泛炎症性疾病（包括休克、缺血再灌注损伤、神经退行性疾病和辐射损伤）的靶向eCIRP的潜在治疗策略。
