Research Paper Volume 15, Issue 21 pp 12618—12632
High-mobility group box-1 impedes skeletal muscle regeneration via downregulation of Pax-7 synthesis by increasing miR-342-5p expression
- 1 Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan
- 2 Department of Physical Medicine and Rehabilitation, China Medical University Hsinchu Hospital, Hsinchu, Taiwan
- 3 Department of Physical Therapy and Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan
- 4 Department of Physical Medicine and Rehabilitation, China Medical University Hospital, Taichung, Taiwan
- 5 School of Chinese Medicine, China Medical University, Taichung, Taiwan
- 6 Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
- 7 Department of Sports Medicine, China Medical University, Taichung, Taiwan
- 8 Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
- 9 Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
- 10 Department of Medical Laboratory Science and Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
- 11 Department of Medical Research, China Medical University Hsinchu Hospital, Hsinchu, Taiwan
Received: June 26, 2023 Accepted: October 15, 2023 Published: November 13, 2023
https://doi.org/10.18632/aging.205202How to Cite
Copyright: © 2023 Ho et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
High mobility group box-1 (HMGB1) is a driver of inflammation in various muscular diseases. In a previous study, we determined that HMGB1 induced the atrophy of skeletal muscle by impairing myogenesis. Skeletal muscle regeneration after injury is dependent on pair box 7 (Pax-7)-mediated myogenic differentiation. In the current study, we determined that the HMGB1-induced downregulation of Pax-7 expression in myoblasts inhibited the regeneration of skeletal muscle. We also determined that HMGB1 inhibits Pax-7 and muscle differentiation by increasing miR-342-5p synthesis via receptors for advanced glycation end-products (RAGE), toll-like receptor (TLR) 2, TLR4, and c-Src signaling pathways. In a mouse model involving glycerol-induced muscle injury, the therapeutic inhibition of HMGB1 was shown to rescue Pax-7 expression and muscle regeneration. The HMGB1/Pax-7 axis is a promising therapeutic target to promote muscular regeneration.