High-mobility group box-1 impedes skeletal muscle regeneration via downregulation of Pax-7 synthesis by increasing miR-342-5p expression

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.

The Role of microRNAs Related to Apoptosis for N-Methyl-d-Aspartic Acid-Induced Neuronal Cell Death in the Murine Retina

“…Unfortunately, we could not clarify the mechanisms and/or the triggers of the expressional changes in miRs by intravitreal NMDA in the present study. Recently, the high-mobility group box-1 (HMGB1)-receptor of advanced glycation end-products (RAGE) axis has been found to be involved in the regulation of miR expression [26,27]. We previously reported that the HMGB1-RAGE axis was involved in neurodegeneration induced by intravitreal NMDA in the retina [28].…”