HMGB1 Promotes In Vitro and In Vivo Skeletal Muscle Atrophy through an IL-18-Dependent Mechanism
Skeletal muscle atrophy occurs due to muscle wasting or reductions in protein associated with aging, injury, and inflammatory processes. High-mobility group box-1 (HMGB1) protein is passively released from necrotic cells and actively secreted by inflammatory cells, and is implicated in the pathogene...
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MDPI AG
2022-12-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/23/3936 |
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| author | Trung-Loc Ho Chih-Hsin Tang Sunny Li-Yun Chang Chun-Hao Tsai Hsien-Te Chen Chen-Ming Su |
| author_facet | Trung-Loc Ho Chih-Hsin Tang Sunny Li-Yun Chang Chun-Hao Tsai Hsien-Te Chen Chen-Ming Su |
| author_sort | Trung-Loc Ho |
| collection | DOAJ |
| description | Skeletal muscle atrophy occurs due to muscle wasting or reductions in protein associated with aging, injury, and inflammatory processes. High-mobility group box-1 (HMGB1) protein is passively released from necrotic cells and actively secreted by inflammatory cells, and is implicated in the pathogenesis of various inflammatory and immune diseases. HMGB1 is upregulated in muscle inflammation, and circulating levels of the proinflammatory cytokine interleukin-18 (IL-18) are upregulated in patients with sarcopenia, a muscle-wasting disease. We examined whether an association exists between HMGB1 and IL-18 signaling in skeletal muscle atrophy. HMGB1-induced increases of IL-18 levels enhanced the expression of muscle atrophy markers and inhibited myogenic marker expression in C2C12 and G7 myoblast cell lines. HMGB1-induced increases of IL-18 production in C2C12 cells involved the RAGE/p85/Akt/mTOR/c-Jun signaling pathway. HMGB1 short hairpin RNA (shRNA) treatment rescued the expression of muscle-specific differentiation markers in murine C2C12 myotubes and in mice with glycerol-induced muscle atrophy. HMGB1 and IL-18 signaling was suppressed in the mice after HMGB1 shRNA treatment. These findings suggest that the HMGB1/IL-18 axis is worth targeting for the treatment of skeletal muscle atrophy. |
| first_indexed | 2024-03-09T17:50:12Z |
| format | Article |
| id | doaj.art-3dfb8234185c4c2bb16f624ec09d97cf |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T17:50:12Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-3dfb8234185c4c2bb16f624ec09d97cf2023-11-24T10:46:17ZengMDPI AGCells2073-44092022-12-011123393610.3390/cells11233936HMGB1 Promotes In Vitro and In Vivo Skeletal Muscle Atrophy through an IL-18-Dependent MechanismTrung-Loc Ho0Chih-Hsin Tang1Sunny Li-Yun Chang2Chun-Hao Tsai3Hsien-Te Chen4Chen-Ming Su5Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung City 40402, TaiwanDepartment of Pharmacology, School of Medicine, China Medical University, Taichung City 40402, TaiwanGraduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung City 40402, TaiwanDepartment of Sports Medicine, China Medical University, Taichung City 40402, TaiwanDepartment of Sports Medicine, China Medical University, Taichung City 40402, TaiwanDepartment of Sports Medicine, China Medical University, Taichung City 40402, TaiwanSkeletal muscle atrophy occurs due to muscle wasting or reductions in protein associated with aging, injury, and inflammatory processes. High-mobility group box-1 (HMGB1) protein is passively released from necrotic cells and actively secreted by inflammatory cells, and is implicated in the pathogenesis of various inflammatory and immune diseases. HMGB1 is upregulated in muscle inflammation, and circulating levels of the proinflammatory cytokine interleukin-18 (IL-18) are upregulated in patients with sarcopenia, a muscle-wasting disease. We examined whether an association exists between HMGB1 and IL-18 signaling in skeletal muscle atrophy. HMGB1-induced increases of IL-18 levels enhanced the expression of muscle atrophy markers and inhibited myogenic marker expression in C2C12 and G7 myoblast cell lines. HMGB1-induced increases of IL-18 production in C2C12 cells involved the RAGE/p85/Akt/mTOR/c-Jun signaling pathway. HMGB1 short hairpin RNA (shRNA) treatment rescued the expression of muscle-specific differentiation markers in murine C2C12 myotubes and in mice with glycerol-induced muscle atrophy. HMGB1 and IL-18 signaling was suppressed in the mice after HMGB1 shRNA treatment. These findings suggest that the HMGB1/IL-18 axis is worth targeting for the treatment of skeletal muscle atrophy.https://www.mdpi.com/2073-4409/11/23/3936HMGB1IL-18inflammationmyogenesisskeletal muscle atrophy |
| spellingShingle | Trung-Loc Ho Chih-Hsin Tang Sunny Li-Yun Chang Chun-Hao Tsai Hsien-Te Chen Chen-Ming Su HMGB1 Promotes In Vitro and In Vivo Skeletal Muscle Atrophy through an IL-18-Dependent Mechanism Cells HMGB1 IL-18 inflammation myogenesis skeletal muscle atrophy |
| title | HMGB1 Promotes In Vitro and In Vivo Skeletal Muscle Atrophy through an IL-18-Dependent Mechanism |
| title_full | HMGB1 Promotes In Vitro and In Vivo Skeletal Muscle Atrophy through an IL-18-Dependent Mechanism |
| title_fullStr | HMGB1 Promotes In Vitro and In Vivo Skeletal Muscle Atrophy through an IL-18-Dependent Mechanism |
| title_full_unstemmed | HMGB1 Promotes In Vitro and In Vivo Skeletal Muscle Atrophy through an IL-18-Dependent Mechanism |
| title_short | HMGB1 Promotes In Vitro and In Vivo Skeletal Muscle Atrophy through an IL-18-Dependent Mechanism |
| title_sort | hmgb1 promotes in vitro and in vivo skeletal muscle atrophy through an il 18 dependent mechanism |
| topic | HMGB1 IL-18 inflammation myogenesis skeletal muscle atrophy |
| url | https://www.mdpi.com/2073-4409/11/23/3936 |
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