在脑出血模型中内皮细胞TRIM 47通过CYLD泛素化降解触发血脑屏障破坏
在脑出血模型中内皮细胞TRIM47通过CYLD泛素化降解触发血脑屏障破坏
作者： 小柯机器人 发布时间：2026/8/13 15:48:38
本期文章：《神经科学通报》：Online/在线发表
重庆医科大学翟瑄小组的一项最新研究发现在脑出血模型中内皮细胞TRIM47通过CYLD泛素化降解触发血脑屏障破坏。2026年8月12日，国际知名学术期刊《神经科学通报》发表了这一成果。
小组发现TRIM47在脑出血后显著上调，并主要在内皮细胞中表达。内皮特异性Trim47缺失通过减少异常血管面积和直径，增加周细胞覆盖，使血肿周围血管重构正常化，从而保持血脑屏障完整性，改善功能完善，减少神经元死亡，促进神经系统恢复。机制上，TRIM47与CYLD结合并促进其泛素化和降解，导致NF-κB和P38/JNK-MAPK信号的激活和神经血管损伤。内皮细胞CYLD过表达重现了Trim47缺乏的保护作用，而CYLD敲低则消除了这些作用，证实了CYLD是一个关键的下游介质。重要的是，AAV介导的Trim47敲低恢复了脑出血后的血管完整性并改善了预后。这些发现确定内皮TRIM47是血脑屏障修复和神经血管恢复的潜在治疗靶点。
据介绍，血脑屏障（BBB）破坏是脑出血（ICH）后神经功能障碍的主要驱动因素；然而，其机制尚不清楚。
附：英文原文
Title: Endothelial Cell TRIM47 Triggers Blood–Brain Barrier Disruption via CYLD Ubiquitination Degradation in an Intracerebral Hemorrhage Model
Author: Li, Qian, Ru, Xue, Li, Chenyang, He, Yaying, Yang, Baohui, Li, Xuemei, Zhai, Xuan
Issue&Volume: 2026-08-12
Abstract: Blood-brain barrier (BBB) disruption is a major driver of neurological deficits after intracerebral hemorrhage (ICH); however, its mechanisms remain unclear. Here, we found that TRIM47 was markedly upregulated after ICH and predominantly expressed in endothelial cells. Endothelial-specific Trim47 deletion normalized peri-hematoma vascular remodeling by reducing the abnormal vascular area and diameter and increasing pericyte coverage, thereby preserving BBB integrity, improving perfusion, reducing neuronal death, and enhancing neurological recovery. Mechanistically, TRIM47 binds to cylindromatosis (CYLD) and promotes its ubiquitination and degradation, leading to activation of NF-κB and P38/JNK-MAPK signaling and neurovascular injury. Endothelial CYLD overexpression reproduced the protective effects of Trim47 deficiency, whereas CYLD knockdown abrogated these effects, confirming that CYLD is a key downstream mediator. Importantly, AAV-mediated Trim47 knockdown restored vascular integrity and improved outcomes after ICH. These findings identify endothelial TRIM47 as a potential therapeutic target for BBB repair and neurovascular recovery.
DOI: 10.1007/s12264-026-01692-5
Source: https://link.springer.com/article/10.1007/s12264-026-01692-5