hUMSC-Exosomes suppress TREM1-p38 MAPK signaling via HMGB1-dependent mechanisms to reprogram microglial function and promote neuroprotection in ischemic stroke
Our findings delineate a novel HMGB1-TREM1-p38 MAPK axis through which hUMSC-Exos mitigate post-stroke neuroinflammation. By delivering HMGB1, hUMSC-Exos inhibit TREM1-dependent NF-κB/p38 activation, reprogram microglial function, and confer neuroprotection. Validated across in vivo, primary, and BV2 microglial models, and supported by multi-omics analyses, this study establishes hUMSC-Exos as a promising cell-free therapy targeting microglial reprogramming for ischemic stroke recovery.
Authors
- Zhuohang Liu
- Zhiwen Jiang (ORCID: https://orcid.org/0000-0003-3576-2534)
- Jing Zhao (ORCID: https://orcid.org/0000-0001-5197-9181)
- Min Chu (ORCID: https://orcid.org/0000-0003-2973-8386)
- Rong Ji (ORCID: https://orcid.org/0000-0002-1724-5253)
- Yong Wang (ORCID: https://orcid.org/0000-0002-8653-514X)
- Zengyu Zhang
Institutions
- Sun Yat-sen University (CN)
- Shanghai Jiao Tong University (CN)
- Fudan University (CN)
- Minhang District Central Hospital (CN)
- Zhongshan Hospital (CN)
- The First Affiliated Hospital, Sun Yat-sen University (CN)
- Huashan Hospital (CN)
- YangPu Geriatric Hospital (CN)
Publication Details
- Journal
- Journal of Nanobiotechnology
- Published
- 2025-08-19
- DOI
- https://doi.org/10.1186/s12951-025-03652-z
- Citations
- 5
- Primary Topic
- Inflammation biomarkers and pathways
- Type
- article
- Field-Weighted Citation Impact
- 3.99
Funders
- National Natural Science Foundation of China