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Research Paper|Volume 14, Issue 24|pp 9860—9876

C-C motif chemokine ligand 2 promotes myogenesis of myoblasts via the AKT-mTOR pathway

Mi Kyung Kwak1, Eun Suk Ha1, Jiwoo Lee1, Yun Mi Choi1, Beom-Jun Kim2, Eun-Gyoung Hong1
  • 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong-Si, Gyeonggi-Do 18450, Korea
  • 2Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Songpa-Gu, Seoul 05505, Korea
Received: June 29, 2022Accepted: November 30, 2022Published: December 27, 2022
https://doi.org/10.18632/aging.204451

Copyright: © 2022 Kwak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Muscle mass decreases with aging, while the C-C motif chemokine ligand 2 (CCL2) increases with aging; in this context, CCL2 can be considered a potential aging-promoting factor. Thus, CCL2 knockout mice are expected to exhibit anti-aging effects including protection against loss of muscle mass. However, instead, muscle amount and recovery of damaged muscles are decreased in CCL2 knockout mice. Therefore, we hypothesized that increasing CCL2 in the elderly might be related to compensation for loss of muscle mass. To confirm the relationship between muscle and CCL2, we sought to establish the role of CCL2 in C2C12 cells and Human Skeletal Muscle Myoblast (HSMM) cells. The myotube (MT) fusion index increased with CCL2 compared to 5day CCL2 vehicle only (27.0 % increase, P<0.05) in immunocytochemistry staining (ICC) data. CCL2 also restored MTs atrophy caused by dexamethasone (21.8 % increase, P<0.0001). p-mTOR/mTOR and p-AKT/total AKT increased with CCL2 compared to CCL2 vehicle only (18.3 and 30.5% increase respectively, P<0.05) and decreased with CCR2-siRNA compared to CCL2 (38.9 % (P<0.05) and 56.7% (P<0.005) reduction respectively). In conclusion, CCL2 positively affects myogenesis by CCR2 via AKT-mTOR signaling pathways. CCL2 might have potential as a therapeutic target for low muscle mass and muscle recovery.