Schwann cells-derived exosomal miR-21 participates in high glucose regulation of neurite outgrowth
Yu-pu Liu,
Ming-yue Tian,
Yi-duo Yang,
Han Li,
Tian-tian Zhao,
Jing Zhu,
Fang-fang Mou,
Guo-hong Cui,
Hai-dong Guo,
Shui-jin Shao
Affiliations
Yu-pu Liu
Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China
Ming-yue Tian
Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Yi-duo Yang
Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Han Li
Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Tian-tian Zhao
Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Jing Zhu
Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Fang-fang Mou
Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Guo-hong Cui
Department of Neurology, Shanghai No. 9 People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China; Corresponding author
Hai-dong Guo
Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Corresponding author
Shui-jin Shao
Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Corresponding author
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.