Abstract: FR-PO813
Electric Acupuncture Mimics Exercise to Ameliorate Muscle Wasting by Promoting Angiogenesis and Neurogenesis in CKD
Session Information
- Health Maintenance, Nutrition, Metabolism - II
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Health Maintenance, Nutrition, and Metabolism
- 1500 Health Maintenance, Nutrition, and Metabolism
Authors
- Su, Zhen, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
- Luo, Xiaomao, Emory University, Atlanta, Georgia, United States
- Bian, Shuyang, Emory University, Atlanta, Georgia, United States
- Cai, Hui, Emory University, Atlanta, Georgia, United States
- Wang, Xiaonan H., Emory University, Atlanta, Georgia, United States
Background
Our previous study demonstrated that acupuncture with low frequency electrical stimulation (Acu/LFES) attenuates skeletal muscle atrophy by improving muscle progenitor cells regeneration. The present study examines whether Acu/LFES improves revascularization, innervation, and protein anabolism in muscle of chronic kidney disease (CKD) mice.
Methods
CKD was induced by the 5/6 nephrectomy. Acu/LFES was applied in hindlimbs of CKD mice. Acu/LFES points were selected by WHO Standard Acupuncture classification. Proteins from hindlimb (gastrocnemius), forelimb (triceps brachii) and back (longissimus) muscles were isolated at 0.5, 6, 24, 48 and 72 hours after Acu-LFES therapy. Protein synthesis was measured by the surface-sensing of translation (SUnSET) assay. Exosomes were isolated using serial centrifugation and subjected to microRNA deep sequencing. NanoSight was used to measure exocomes concentration. The microRNA library was validated using a High Sensitivity DNA chip.
Results
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 after treatment. These increases were accompanied with increased phosphorylation of mTORC1 and 4EBP-1. Myogenesis markers, Pax7, myoD and myogenin were significantly upregulated. 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, which suggests a mechanism in which downregulation of these two miRNAs results in expanding VEGF and ENO2 leading to accelerate revascularization and innervation.
Conclusion
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. Our study provides strong mechanistic insights for Acu/LFES treatment of muscle atrophy in CKD.
Funding
- Private Foundation Support