Electric Acupuncture Mimics Exercise to Promote Myogenesis, Angiogenesis and Neurogenesis

Author(s): Zhen Su, Manshu Yu, Ying Huang, Janet D Klein, Shuyang Simon Bian, Yijin Huang, Faten Hassounah, Xinwang Chen, Xiyan Gao, Hui Cai, Xiaonan H Wang

Our previous study demonstrated that acupuncture with low frequency electrical stimulation (Acu-LFES) attenuates skeletal muscle atrophy by improving muscle progenitor cell regeneration. The present study examines whether Acu-LFES improves revascularization, innervation, and protein anabolism in muscle of chronic kidney disease (CKD) mice. CKD was induced by the 5/6 nephrectomy in mice. Acu-LFES treatment was applied in hindlimbs of CKD mice. Pro-teins from hindlimb (gastrocnemius), forelimb (triceps brachii) and back (longissimus) muscles were isolated and Pro-tein synthesis was measured by the surface-sensing of translation (SUnSET) assay. Exosomes were isolated using serial centrifugation and concentration and size of the collected exosomes were measured using a NanoSight instrument. The mature microRNA library was validated using a High Sensitivity DNA chip. Protein synthesis was enhanced in the Acu/LFES-treated gastrocnemius; however, in non-Acu/LFES treated muscles, triceps brachii and longissimus, protein synthesis was also significantly increased. These increases were accompanied with increased myogenesis markers myoD and myogenin. The mRNA expression of PDGF and ENO2 were enhanced by Acu/LFES. The protein amount of Igf-1, Igf-1 receptor, VEGF (a protein that stimulates the formation of blood vessels), and peripherin (expressed mainly in the nervous system) were also increased by Acu/LFES. Deep sequencing revealed that miR-5107-5p and miR-30-5p were sharply decreased in serum exosomes of Acu/LFES mice. Using a luciferase reporter assay, we demonstrated that miR-5107-5p directly inhibits VEGF, and miR-30-5p inhibits ENO2. Conclusions: Acu-LFES treatment increases myogenesis, angiogenesis and neurogenesis, as well as protein synthesis. Acu/LFES inhibits miR-5107 and miR-30, resulting in increased VEGF and ENO2 contributing to these processes.