Scholarlink

Objective <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusion <p>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.</p> Graphical abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Engineering RVG-modified exosomes for targeting TGF-β1 signaling in stroke recovery

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月29日

查看全文
  • Wang Zhao,
  • Lei Hao,
  • Jiangwei Zhang,
  • Jun Zhu,
  • Jia Kuang,
  • Meibiao Zhang,
  • Yonggang Zhang,
  • Xiaoxing Xiong,
  • Zhao Yang

摘要

Objective

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.

Methods

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.

Results

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.

Conclusion

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.

Graphical abstract