Qin Yuting, Liao Shuanglin, Sun Jianbo, Ye Huiyun, Li Jiafu, Pan Jiahui, He Junbing, Xia Zhengyuan, Shao Yiming
Dongguan Key Laboratory of Sepsis Translational Medicine, The Intensive Care Unit, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, Guangdong, People's Republic of China.
Dongguan Key Laboratory of Chronic Inflammatory Diseases, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, Guangdong, People's Republic of China.
J Inflamm Res. 2025 Feb 6;18:1787-1813. doi: 10.2147/JIR.S501856. eCollection 2025.
Reversion inducing cysteine rich protein with kazal motifs (RECK), a Kazal motif-containing protein, regulates pro-inflammatory cytokines production, migration of inflammatory cells, vascular endothelial growth factor (VEGF) and Wnt pathways and plays critical roles in septic inflammatory storms and vascular endothelial dysfunction. Recently, RECK has been defined as the negative regulator of adisintegrin and metalloproteinases (ADAMs) and matrix metalloproteinases (MMPs), which are both membrane "molecular scissors" and aggravate the poor prognosis of sepsis. To better understand the roles of RECK and the related mechanisms, we make here a systematic and in-depth review of RECK. We first summarize the findings on structural characteristics of RECK protein and the regulation at the transcription, post-transcription, or protein level of RECK. Then, we discuss the roles of RECK in inflammation, infection, and vascular injury by focusing on the RECK function on ADAMs and MMPs, as well as the pathways of VEGF, WNT, angiopoietin, and notch signaling. In conclusion, RECK participation as a guardian in the development of sepsis provides insight into the strategies of precisely intervening in RECK dysregulationfor the treatment of sepsis.
含Kazal基序的逆转诱导富含半胱氨酸蛋白（RECK）是一种含Kazal基序的蛋白，它调节促炎细胞因子的产生、炎症细胞的迁移、血管内皮生长因子（VEGF）和Wnt信号通路，在脓毒症炎症风暴和血管内皮功能障碍中起关键作用。最近，RECK被定义为去整合素和金属蛋白酶（ADAMs）以及基质金属蛋白酶（MMPs）的负调节因子，这两种酶都是膜“分子剪刀”，会加重脓毒症的不良预后。为了更好地理解RECK的作用及相关机制，我们在此对RECK进行系统深入的综述。我们首先总结了关于RECK蛋白结构特征以及RECK在转录、转录后或蛋白水平调控的研究结果。然后，我们通过关注RECK对ADAMs和MMPs的功能以及VEGF、WNT、血管生成素和Notch信号通路，来讨论RECK在炎症、感染和血管损伤中的作用。总之，RECK作为脓毒症发展的守护者参与其中，为精准干预RECK失调以治疗脓毒症提供了策略思路。
