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Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10683625 | PMC |
| http://dx.doi.org/10.18632/aging.205202 | DOI Listing |
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