Endothelial Cell TRIM47 Triggers Blood-Brain Barrier Disruption via CYLD Ubiquitination Degradation in an Intracerebral Hemorrhage Model.

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.