设计RVG修饰的外泌体，以靶向TGF-β1信号传导，促进卒中恢复
Engineering RVG-modified exosomes for targeting TGF-β1 signaling in stroke recovery.
摘要(中文译文)
为探究缺血性卒中后TGF-β1信号在星形胶质细胞-神经元相互作用中的作用，并开发一种用于促进神经修复的脑靶向工程化外泌体系统EXO-RVG-SD208。利用公共数据集和转录组分析表征卒中后TGF-β1的动态变化，并通过GO、KEGG和WGCNA分析鉴定关键靶点。构建脑靶向工程化外泌体EXO-RVG-SD208并表征其理化性质。在氧糖剥夺/复氧（OGD/R）及神经元-星形胶质细胞共培养模型中评估其对星形胶质细胞TGF-β1/Smad2/3通路的抑制作用及神经再生潜力。进一步在大脑中动脉闭塞/再灌注（MCAO/R）小鼠模型中评估治疗效果。通过整合多组学分析探讨参与神经修复的下游机制。TGF-β1在卒中后显著上调，且主要来源于星形胶质细胞，其与神经炎症和神经可塑性受损密切相关。EXO-RVG-SD208有效抑制TGF-β1/Smad2/3通路的激活，促进星形胶质细胞表型重塑，增强神经元突触活动，并改善MCAO/R小鼠的功能恢复。多组学分析进一步表明，其治疗效应与mTOR、BDNF和MAPK相关通路的调控有关。EXO-RVG-SD208有效将TGF-β1抑制剂递送至脑内，抑制星形胶质细胞TGF-β1/Smad2/3激活，促进星形胶质细胞-神经元重塑、突触重建和神经功能恢复，为卒中康复提供了一种有前景的纳米递送策略。
Abstract
To investigate the role of TGF-β1 signaling in astrocyte-neuron interactions after ischemic stroke and to develop a brain-targeted engineered exosome system, EXO-RVG-SD208, for promoting neural repair. Public datasets and transcriptomic analyses were used to characterize the dynamic changes of TGF-β1 after stroke, and key targets were identified through GO, KEGG, and WGCNA analyses. A brain-targeted engineered exosome, EXO-RVG-SD208, was constructed and characterized for its physicochemical properties. Its inhibitory effect on the TGF-β1/Smad2/3 pathway in astrocytes and its neuroregenerative potential were evaluated in oxygen-glucose deprivation/reoxygenation (OGD/R) and neuron-astrocyte co-culture models. Therapeutic efficacy was further assessed in a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model. Integrated multi-omics analyses were performed to explore the downstream mechanisms involved in neural repair. TGF-β1 was markedly upregulated after stroke and was predominantly derived from astrocytes, where it was closely associated with neuroinflammation and impaired neuroplasticity. EXO-RVG-SD208 effectively inhibited activation of the TGF-β1/Smad2/3 pathway, promoted astrocyte phenotypic remodeling, enhanced neuronal synaptic activity, and improved functional recovery in MCAO/R mice. Multi-omics analyses further indicated that the therapeutic effects were associated with the regulation of mTOR, BDNF, and MAPK-related pathways. EXO-RVG-SD208 effectively delivered TGF-β1 inhibitor to the brain, suppressed astrocytic TGF-β1/Smad2/3 activation, facilitated astrocyte-neuron remodeling, synaptic reconstruction, and neural functional recovery, presenting a promising nanodelivery strategy for stroke rehabilitation.
如何引用
AMA
Wang Zhao, Lei Hao, Jiangwei Zhang, Jun Zhu, Jia Kuang, Meibiao Zhang, et al. Engineering RVG-modified exosomes for targeting TGF-β1 signaling in stroke recovery.. Journal of translational medicine. 2026; doi:10.1186/s12967-026-08271-2.
APA
Wang Zhao, Lei Hao, Jiangwei Zhang, Jun Zhu, Jia Kuang, Meibiao Zhang, et al (2026). Engineering RVG-modified exosomes for targeting TGF-β1 signaling in stroke recovery.. Journal of translational medicine. https://doi.org/10.1186/s12967-026-08271-2
GB/T 7714
Wang Zhao, Lei Hao, Jiangwei Zhang, Jun Zhu, Jia Kuang, Meibiao Zhang, et al. Engineering RVG-modified exosomes for targeting TGF-β1 signaling in stroke recovery.[J]. Journal of translational medicine, 2026 doi:10.1186/s12967-026-08271-2.
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