Transcriptional Co‐Activator With PDZ Binding Motif (TAZ) Inhibits Dexamethasone‐Induced Muscle Atrophy via mTOR Signalling
ABSTRACT Background Glucocorticoid therapy has a beneficial effect in several diseases, but chronic treatment has adverse effects, including muscle atrophy, which refers to the gradual decrease in muscle mass, size and strength. It is important to know how the muscle atrophy occurs, but the underlyi...
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| Format: | Article |
| Language: | English |
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Wiley
2025-04-01
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| Series: | Journal of Cachexia, Sarcopenia and Muscle |
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| Online Access: | https://doi.org/10.1002/jcsm.13790 |
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| author | Kyung Min Kim Ho Taek Oh Youjin Do Gi Don Yoo Woong Heo Jeekeon Park Hyejin Yang Suh Jin Yoon Mi Ran Byun Eun Sook Hwang Jeong‐Ho Hong |
| author_facet | Kyung Min Kim Ho Taek Oh Youjin Do Gi Don Yoo Woong Heo Jeekeon Park Hyejin Yang Suh Jin Yoon Mi Ran Byun Eun Sook Hwang Jeong‐Ho Hong |
| author_sort | Kyung Min Kim |
| collection | DOAJ |
| description | ABSTRACT Background Glucocorticoid therapy has a beneficial effect in several diseases, but chronic treatment has adverse effects, including muscle atrophy, which refers to the gradual decrease in muscle mass, size and strength. It is important to know how the muscle atrophy occurs, but the underlying mechanism is not yet fully understood. This study shows that dexamethasone decreases levels of the transcriptional co‐activator with PDZ binding motif (TAZ), which facilitates dexamethasone‐induced muscle atrophy. Methods To induce muscle atrophy, C2C12 myotubes were treated with dexamethasone, and mice were fed with water containing dexamethasone. Muscle atrophy was analysed for the expression of myosin heavy chain, MuRF1 and Atrogin‐1 using immunofluorescence staining, immunoblot analysis and qRT‐PCR. Muscle tissue was analysed by haematoxylin and eosin staining. Adeno‐associated virus was used for overexpression of wild‐type and mutant TAZ. Results TAZ levels decrease in dexamethasone‐treated mice (0.36‐fold, p < 0.001) and C2C12 myotubes (0.44‐fold, p = 0.024). Overexpression of the TAZ mutant, which resists its proteolytic degradation, inhibits dexamethasone‐induced muscle atrophy. Atrogin‐1 and MuRF1 interact with TAZ and facilitate its degradation in dexamethasone‐treated C2C12 myotubes. TAZ mutant stimulates protein synthesis through activation of mTOR signalling via induction of RhebL1 (DEX; Con vs, TAZ4SA: 5.1‐fold, p < 0.001) in dexamethasone‐treated mice. Ginsenoside Rb3 increases TAZ levels in dexamethasone‐treated mice (1.49‐fold, p = 0.007) and C2C12 myotubes (1.63‐fold, p = 0.01), which stimulates mTOR signalling and inhibits dexamethasone‐induced muscle atrophy. Conclusions Our results demonstrate a novel regulatory mechanism of dexamethasone‐induced muscle atrophy by TAZ, suggesting that stabilisation of TAZ in muscle cells ameliorates the muscle atrophy. These results suggest that TAZ may be a drug target for the dexamethasone‐induced muscle atrophy. |
| format | Article |
| id | doaj-art-fa74ce3e3ac144efa2d836c508cdf1d3 |
| institution | DOAJ |
| issn | 2190-5991 2190-6009 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
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| series | Journal of Cachexia, Sarcopenia and Muscle |
| spelling | doaj-art-fa74ce3e3ac144efa2d836c508cdf1d32025-08-20T03:10:42ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092025-04-01162n/an/a10.1002/jcsm.13790Transcriptional Co‐Activator With PDZ Binding Motif (TAZ) Inhibits Dexamethasone‐Induced Muscle Atrophy via mTOR SignallingKyung Min Kim0Ho Taek Oh1Youjin Do2Gi Don Yoo3Woong Heo4Jeekeon Park5Hyejin Yang6Suh Jin Yoon7Mi Ran Byun8Eun Sook Hwang9Jeong‐Ho Hong10Division of Life Sciences Korea University Seoul South KoreaDivision of Life Sciences Korea University Seoul South KoreaDivision of Life Sciences Korea University Seoul South KoreaDivision of Life Sciences Korea University Seoul South KoreaDivision of Life Sciences Korea University Seoul South KoreaDivision of Life Sciences Korea University Seoul South KoreaDivision of Life Sciences Korea University Seoul South KoreaCollege of Pharmacy and Graduate School of Pharmaceutical Sciences Ewha Woman's University Seoul South KoreaCollege of Pharmacy Daegu Catholic University Gyeongsan South KoreaCollege of Pharmacy and Graduate School of Pharmaceutical Sciences Ewha Woman's University Seoul South KoreaDivision of Life Sciences Korea University Seoul South KoreaABSTRACT Background Glucocorticoid therapy has a beneficial effect in several diseases, but chronic treatment has adverse effects, including muscle atrophy, which refers to the gradual decrease in muscle mass, size and strength. It is important to know how the muscle atrophy occurs, but the underlying mechanism is not yet fully understood. This study shows that dexamethasone decreases levels of the transcriptional co‐activator with PDZ binding motif (TAZ), which facilitates dexamethasone‐induced muscle atrophy. Methods To induce muscle atrophy, C2C12 myotubes were treated with dexamethasone, and mice were fed with water containing dexamethasone. Muscle atrophy was analysed for the expression of myosin heavy chain, MuRF1 and Atrogin‐1 using immunofluorescence staining, immunoblot analysis and qRT‐PCR. Muscle tissue was analysed by haematoxylin and eosin staining. Adeno‐associated virus was used for overexpression of wild‐type and mutant TAZ. Results TAZ levels decrease in dexamethasone‐treated mice (0.36‐fold, p < 0.001) and C2C12 myotubes (0.44‐fold, p = 0.024). Overexpression of the TAZ mutant, which resists its proteolytic degradation, inhibits dexamethasone‐induced muscle atrophy. Atrogin‐1 and MuRF1 interact with TAZ and facilitate its degradation in dexamethasone‐treated C2C12 myotubes. TAZ mutant stimulates protein synthesis through activation of mTOR signalling via induction of RhebL1 (DEX; Con vs, TAZ4SA: 5.1‐fold, p < 0.001) in dexamethasone‐treated mice. Ginsenoside Rb3 increases TAZ levels in dexamethasone‐treated mice (1.49‐fold, p = 0.007) and C2C12 myotubes (1.63‐fold, p = 0.01), which stimulates mTOR signalling and inhibits dexamethasone‐induced muscle atrophy. Conclusions Our results demonstrate a novel regulatory mechanism of dexamethasone‐induced muscle atrophy by TAZ, suggesting that stabilisation of TAZ in muscle cells ameliorates the muscle atrophy. These results suggest that TAZ may be a drug target for the dexamethasone‐induced muscle atrophy.https://doi.org/10.1002/jcsm.13790dexamethasoneginsenosidemTORmuscle atrophy |
| spellingShingle | Kyung Min Kim Ho Taek Oh Youjin Do Gi Don Yoo Woong Heo Jeekeon Park Hyejin Yang Suh Jin Yoon Mi Ran Byun Eun Sook Hwang Jeong‐Ho Hong Transcriptional Co‐Activator With PDZ Binding Motif (TAZ) Inhibits Dexamethasone‐Induced Muscle Atrophy via mTOR Signalling Journal of Cachexia, Sarcopenia and Muscle dexamethasone ginsenoside mTOR muscle atrophy |
| title | Transcriptional Co‐Activator With PDZ Binding Motif (TAZ) Inhibits Dexamethasone‐Induced Muscle Atrophy via mTOR Signalling |
| title_full | Transcriptional Co‐Activator With PDZ Binding Motif (TAZ) Inhibits Dexamethasone‐Induced Muscle Atrophy via mTOR Signalling |
| title_fullStr | Transcriptional Co‐Activator With PDZ Binding Motif (TAZ) Inhibits Dexamethasone‐Induced Muscle Atrophy via mTOR Signalling |
| title_full_unstemmed | Transcriptional Co‐Activator With PDZ Binding Motif (TAZ) Inhibits Dexamethasone‐Induced Muscle Atrophy via mTOR Signalling |
| title_short | Transcriptional Co‐Activator With PDZ Binding Motif (TAZ) Inhibits Dexamethasone‐Induced Muscle Atrophy via mTOR Signalling |
| title_sort | transcriptional co activator with pdz binding motif taz inhibits dexamethasone induced muscle atrophy via mtor signalling |
| topic | dexamethasone ginsenoside mTOR muscle atrophy |
| url | https://doi.org/10.1002/jcsm.13790 |
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