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

Trung-Loc Ho¹, Yu-Liang Lai^2,^3,⁴, Chin-Jung Hsu^5,⁶, Chen-Ming Su⁷, Chih-Hsin Tang^1,^8,^9,^10,¹¹

¹Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan
²Department of Physical Medicine and Rehabilitation, China Medical University Hsinchu Hospital, Hsinchu, Taiwan
³Department of Physical Therapy and Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan
⁴Department of Physical Medicine and Rehabilitation, China Medical University Hospital, Taichung, Taiwan
⁵School of Chinese Medicine, China Medical University, Taichung, Taiwan
⁶Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
⁷Department of Sports Medicine, China Medical University, Taichung, Taiwan
⁸Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
⁹Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
¹⁰Department of Medical Laboratory Science and Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
¹¹Department of Medical Research, China Medical University Hsinchu Hospital, Hsinchu, Taiwan

* Equal contribution

Received: June 26, 2023Accepted: October 15, 2023Published: November 13, 2023

https://doi.org/10.18632/aging.205202

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.