Extracellular vesicle-mediated restraint of hepatic CD74–NF-κB repairs diabetic neuropathy

Diabetic peripheral neuropathy (DPN) affects up to half of people with diabetes and lacks disease-modifying therapy. Here, we profiled MSC-EV biodistribution and multiomic programs across diabetic models, with key nerve repair established in db/db mice and corroborated in high-fat diet/streptozotocin- and methionine-choline-deficient mice. Systemically administered EVs predominantly accumulated in the liver and improved peripheral nerve structure and function, with benefits supported by glycemia-controlled or glycemia-adjusted analyses rather than being fully explained by systemic glycemic changes. EV treatment was associated with reduced circulating injury markers, attenuated spinal inflammatory responses, and improved endothelial junction integrity. Mechanistically, EV-encapsulated miR-24-3p repressed hepatic CD74, coinciding with reduced MHC II/NF-κB activity in macrophages. Hepatic CD74 overexpression promoted systemic inflammation and peripheral nerve injury, whereas pharmacologic NF-κB inhibition recapitulated EV-associated benefits. Together, these data define a liver-to-nerve causal axis and support EV-mediated restraint of hepatic CD74-NF-κB signaling as a cross-organ strategy for DPN repair.

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Publication Details

Journal
Science Advances
Published
2026-10-30
DOI
https://doi.org/10.1126/sciadv.aei3312
Primary Topic
Extracellular vesicles in disease
Type
article
Field-Weighted Citation Impact
0.00

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article

Extracellular vesicle-mediated restraint of hepatic CD74–NF-κB repairs diabetic neuropathy

Andrius Baskys, Qianfa Long, Panpan Meng, Qiang Luo et al.
4 links
Science Advances
Extracellular vesicles in disease
article

Extracellular vesicle-mediated restraint of hepatic CD74–NF-κB repairs diabetic neuropathy

Andrius Baskys, Qianfa Long, Panpan Meng, Qiang Luo, Yue Hei, Lianbing Zhang, Xia Li, Yabin Wang, 思柔 黄, Jinyun Niu, Junxiu Xi, Mingjun Hu, Zhiying Zou, Jiahui Zhao, Yu Miao, Hao Yang
article en

Abstract

Diabetic peripheral neuropathy (DPN) affects up to half of people with diabetes and lacks disease-modifying therapy. Here, we profiled MSC-EV biodistribution and multiomic programs across diabetic models, with key nerve repair established in db/db mice and corroborated in high-fat diet/streptozotocin- and methionine-choline-deficient mice. Systemically administered EVs predominantly accumulated in the liver and improved peripheral nerve structure and function, with benefits supported by glycemia-controlled or glycemia-adjusted analyses rather than being fully explained by systemic glycemic changes. EV treatment was associated with reduced circulating injury markers, attenuated spinal inflammatory responses, and improved endothelial junction integrity. Mechanistically, EV-encapsulated miR-24-3p repressed hepatic CD74, coinciding with reduced MHC II/NF-κB activity in macrophages. Hepatic CD74 overexpression promoted systemic inflammation and peripheral nerve injury, whereas pharmacologic NF-κB inhibition recapitulated EV-associated benefits. Together, these data define a liver-to-nerve causal axis and support EV-mediated restraint of hepatic CD74-NF-κB signaling as a cross-organ strategy for DPN repair.

Science AdvancesVol. 12(44)
Northwestern Polytechnical University (CN), Chinese PLA General Hospital (CN), Xian Central Hospital (CN), Xijing Hospital (CN), Xi'an Jiaotong University (CN), Western University of Health Sciences (US), Air Force Medical University (CN)
National Natural Science Foundation of China
Good health and well-being
Openalex Percentile: Top 22%
Extracellular vesicles in disease
DOIOpen Access PDFOpenAlex
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