Exosomes Derived From Schwann Cells Ameliorate Peripheral Neuropathy in Type 2 Diabetic Mice
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- Lei Wang
- Department of Neurology, Henry Ford Hospital, Detroit, MI
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- Michael Chopp
- Department of Neurology, Henry Ford Hospital, Detroit, MI
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- Alexandra Szalad
- Department of Neurology, Henry Ford Hospital, Detroit, MI
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- XueRong Lu
- Department of Neurology, Henry Ford Hospital, Detroit, MI
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- Yi Zhang
- Department of Neurology, Henry Ford Hospital, Detroit, MI
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- Xinli Wang
- Department of Neurology, Henry Ford Hospital, Detroit, MI
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- Pasquale Cepparulo
- Department of Neurology, Henry Ford Hospital, Detroit, MI
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- Mei Lu
- Department of Biostatistics and Research Epidemiology, Henry Ford Hospital, Detroit, MI
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- Chao Li
- Department of Neurology, Henry Ford Hospital, Detroit, MI
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- Zheng Gang Zhang
- Department of Neurology, Henry Ford Hospital, Detroit, MI
抄録
<jats:p>Schwann cell–derived exosomes communicate with dorsal root ganglia (DRG) neurons. The current study investigated the therapeutic effect of exosomes derived from healthy Schwann cells (SC-Exos) on diabetic peripheral neuropathy (DPN). We found that intravenous administration of SC-Exos to type 2 diabetic db/db mice with peripheral neuropathy remarkably ameliorated DPN by improving sciatic nerve conduction velocity and increasing thermal and mechanical sensitivity. These functional improvements were associated with the augmentation of epidermal nerve fibers and remyelination of sciatic nerves. Quantitative RT-PCR and Western blot analysis of sciatic nerve tissues showed that SC-Exo treatment reversed diabetes-reduced mature form of miRNA (miR)-21, -27a, and -146a and diabetes-increased semaphorin 6A (SEMA6A); Ras homolog gene family, member A (RhoA); phosphatase and tensin homolog (PTEN); and nuclear factor-κB (NF-κB). In vitro data showed that SC-Exos promoted neurite outgrowth of diabetic DRG neurons and migration of Schwann cells challenged by high glucose. Collectively, these novel data provide evidence that SC-Exos have a therapeutic effect on DPN in mice and suggest that SC-Exo modulation of miRs contributes to this therapy.</jats:p>
収録刊行物
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- Diabetes
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Diabetes 69 (4), 749-759, 2020-01-08
American Diabetes Association