Extracellular vesicle-mediated restraint of hepatic CD74–NF-κB repairs diabetic neuropathy
9 affiliations
- 1Key Laboratory of Central Nervous System Diseases, Xi’an Jiaotong University, Xi’an 71003, China.
- 2Department of Neurosurgery, Xi’an Central Hospital, Xi’an Jiaotong University, Xi’an 71003, China.
- 3Shaanxi LonEV Biotechnology Limited Company, Xi’an 712046, China.
- 4Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi’an, 710072 Shaanxi, China.
- 5Department of Nuclear Medicine, Xi’an Central Hospital, Xi’an Jiaotong University, Xi’an 71003, China.
- 6Western University of Health Sciences Medical Center, Specialty Clinics, WesternU Health, 795 E Second Street, Suite 7, 2nd Floor, Pomona, CA 91766, USA.
- 7MoodNote LLC, P.O. Box 9287, Newport Beach, CA 92658, USA.
- 86th Department of Health Care, The Second Medical Center and National Clinical Research Center for Geriatric Diseases, PLA General Hospital, Beijing 100853, China.
- 9Department of Neurosurgery, Xijing Hospital, Air Force Medical University, Xi’an 710032, China.
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.
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BibTeX
@article{yang2026extracellular,
title = {{Extracellular vesicle-mediated restraint of hepatic CD74–NF-κB repairs diabetic neuropathy}},
author = {Hao Yang and Yu Miao and Panpan Meng and Jinyun Niu and Junxiu Xi and Zhiying Zou and Yue Hei and Jiahui Zhao and Qiang Luo and Sirou Huang and Mingjun Hu and Lianbing Zhang and Andrius Baskys and Yabin Wang and Xia Li and Qianfa Long},
journal = {Science Advances},
year = {2026},
month = oct,
doi = {10.1126/sciadv.aei3312},
url = {https://www.science.org/doi/abs/10.1126/sciadv.aei3312},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Extracellular vesicle-mediated restraint of hepatic CD74–NF-κB repairs diabetic neuropathy
AU - Hao Yang
AU - Yu Miao
AU - Panpan Meng
AU - Jinyun Niu
AU - Junxiu Xi
AU - Zhiying Zou
AU - Yue Hei
AU - Jiahui Zhao
AU - Qiang Luo
AU - Sirou Huang
AU - Mingjun Hu
AU - Lianbing Zhang
AU - Andrius Baskys
AU - Yabin Wang
AU - Xia Li
AU - Qianfa Long
PY - 2026
DA - 2026/10/30
JO - Science Advances
DO - 10.1126/sciadv.aei3312
UR - https://www.science.org/doi/abs/10.1126/sciadv.aei3312
AB - 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.
SN - 2375-2548
ER -