Schwann cells-derived exosomal miR-21 participates in high glucose regulation of neurite outgrowth

Summary

As a common complication of diabetes, the pathogenesis of diabetic peripheral neuropathy (DPN) is closely related to high glucose but has not been clarified. Exosomes can mediate crosstalk between Schwann cells (SC) and neurons in the peripheral nerve. Herein, we found that miR-21 in serum exosomes from DPN rats was decreased. SC proliferation was inhibited, cell apoptosis was increased, and the expression of miR-21 in cells and exosomes was downregulated when cultured in high glucose. Increasing miR-21 expression reversed these changes, while knockdown of miR-21 led to the opposite results. When co-cultured with exosomes derived from SC exposed to high glucose, neurite outgrowth was inhibited. On the contrary, neurite outgrowth was accelerated when incubated with exosomes rich in miR-21. We further demonstrated that the SC-derived exosomal miR-21 participates in neurite outgrowth probably through the AKT signaling pathway. Thus, SC-derived exosomal miR-21 contributes to high glucose regulation of neurite outgrowth.

Graphical abstract

Highlights

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  The miR-21 was decreased in serum exosomes and sciatic nerve of DPN rats

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  High glucose inhibited SC viability and downregulated the expression of miR-21

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  Exosomes derived from SC cultured in high glucose inhibited the neurite outgrowth

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  SC-derived exosomes rich in miR-21 accelerated the neurite outgrowth of neuron

Abstract

Biological sciences; Neuroscience; Molecular neuroscience; Diabetology