STING protects against cardiac dysfunction and remodelling by blocking autophagy
Abstract Background Heart failure, which is characterized by cardiac remodelling, is one of the most common chronic diseases in the aged. Stimulator of interferon genes (STING) acts as an indispensable molecule modulating immune response and inflammation in many diseases. However, the effects of STI...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-11-01
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| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-021-00793-0 |
| _version_ | 1818932859622129664 |
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| author | Rui Xiong Ning Li Lei Chen Wei Wang Bo Wang Wenyang Jiang Qing Geng |
| author_facet | Rui Xiong Ning Li Lei Chen Wei Wang Bo Wang Wenyang Jiang Qing Geng |
| author_sort | Rui Xiong |
| collection | DOAJ |
| description | Abstract Background Heart failure, which is characterized by cardiac remodelling, is one of the most common chronic diseases in the aged. Stimulator of interferon genes (STING) acts as an indispensable molecule modulating immune response and inflammation in many diseases. However, the effects of STING on cardiomyopathy, especially cardiac remodelling are still largely unknown. This study was designed to investigate whether STING could affect cardiac remodelling and to explore the potential mechanisms. Methods In vivo, aortic binding (AB) surgery was performed to construct the mice model of cardiac remodelling. A DNA microinjection system was used to trigger STING overexpression in mice. The STING mRNA and protein expression levels in mice heart were measured, and the cardiac hypertrophy, fibrosis, inflammation and cardiac function were also evaluated. In vitro, cardiomyocytes stimulated by Ang II and cardiac fibroblasts stimulated by TGF-β to performed to further study effects of STING on cardiac hypertrophy and fibroblast. In terms of mechanisms, the level of autophagy was detected in mice challenged with AB. Rapamycin, a canonical autophagy inducer, intraperitoneal injected into mice to study possible potential pathway. Results In vivo, the STING mRNA and protein expression levels in mice heart challenged with AB for 6 weeks were significantly increased. STING overexpression significantly mitigated cardiac hypertrophy, fibrosis and inflammation, apart from improving cardiac function. In vitro, experiments further disclosed that STING overexpression in cardiomyocytes induced by Ang II significantly inhibited the level of cardiomyocyte cross-section area and the ANP mRNA. Meanwhile, TGF-β-induced the increase of α-SMA content and collagen synthesis in cardiac fibroblasts could be also blocked by STING overexpression. In terms of mechanisms, mice challenged with AB showed higher level of autophagy compared with the normal mice. However, STING overexpression could reverse the activation of autophagy triggered by AB. Rapamycin, a canonical autophagy inducer, offset the cardioprotective effects of STING in mice challenged with AB. Finally, further experiments unveiled that STING may inhibit autophagy by phosphorylating ULK1 on serine757. Conclusions STING may prevent cardiac remodelling induced by pressure overload by inhibiting autophagy, which could be a promising therapeutic target in heart failure. Video Abstract |
| first_indexed | 2024-12-20T04:39:11Z |
| format | Article |
| id | doaj.art-0540ee358583444eb7a494c04aac8a33 |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-12-20T04:39:11Z |
| publishDate | 2021-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-0540ee358583444eb7a494c04aac8a332022-12-21T19:53:10ZengBMCCell Communication and Signaling1478-811X2021-11-0119111310.1186/s12964-021-00793-0STING protects against cardiac dysfunction and remodelling by blocking autophagyRui Xiong0Ning Li1Lei Chen2Wei Wang3Bo Wang4Wenyang Jiang5Qing Geng6Department of Thoracic Surgery, Renmin Hospital of Wuhan UniversityDepartment of Thoracic Surgery, Renmin Hospital of Wuhan UniversityDepartment of Orthopedics, Renmin Hospital of Wuhan UniversityDepartment of Thoracic Surgery, Renmin Hospital of Wuhan UniversityDepartment of Thoracic Surgery, Renmin Hospital of Wuhan UniversityDepartment of Thoracic Surgery, Renmin Hospital of Wuhan UniversityDepartment of Thoracic Surgery, Renmin Hospital of Wuhan UniversityAbstract Background Heart failure, which is characterized by cardiac remodelling, is one of the most common chronic diseases in the aged. Stimulator of interferon genes (STING) acts as an indispensable molecule modulating immune response and inflammation in many diseases. However, the effects of STING on cardiomyopathy, especially cardiac remodelling are still largely unknown. This study was designed to investigate whether STING could affect cardiac remodelling and to explore the potential mechanisms. Methods In vivo, aortic binding (AB) surgery was performed to construct the mice model of cardiac remodelling. A DNA microinjection system was used to trigger STING overexpression in mice. The STING mRNA and protein expression levels in mice heart were measured, and the cardiac hypertrophy, fibrosis, inflammation and cardiac function were also evaluated. In vitro, cardiomyocytes stimulated by Ang II and cardiac fibroblasts stimulated by TGF-β to performed to further study effects of STING on cardiac hypertrophy and fibroblast. In terms of mechanisms, the level of autophagy was detected in mice challenged with AB. Rapamycin, a canonical autophagy inducer, intraperitoneal injected into mice to study possible potential pathway. Results In vivo, the STING mRNA and protein expression levels in mice heart challenged with AB for 6 weeks were significantly increased. STING overexpression significantly mitigated cardiac hypertrophy, fibrosis and inflammation, apart from improving cardiac function. In vitro, experiments further disclosed that STING overexpression in cardiomyocytes induced by Ang II significantly inhibited the level of cardiomyocyte cross-section area and the ANP mRNA. Meanwhile, TGF-β-induced the increase of α-SMA content and collagen synthesis in cardiac fibroblasts could be also blocked by STING overexpression. In terms of mechanisms, mice challenged with AB showed higher level of autophagy compared with the normal mice. However, STING overexpression could reverse the activation of autophagy triggered by AB. Rapamycin, a canonical autophagy inducer, offset the cardioprotective effects of STING in mice challenged with AB. Finally, further experiments unveiled that STING may inhibit autophagy by phosphorylating ULK1 on serine757. Conclusions STING may prevent cardiac remodelling induced by pressure overload by inhibiting autophagy, which could be a promising therapeutic target in heart failure. Video Abstracthttps://doi.org/10.1186/s12964-021-00793-0STINGCardiac remodellingInflammationAutophagyULK1 |
| spellingShingle | Rui Xiong Ning Li Lei Chen Wei Wang Bo Wang Wenyang Jiang Qing Geng STING protects against cardiac dysfunction and remodelling by blocking autophagy Cell Communication and Signaling STING Cardiac remodelling Inflammation Autophagy ULK1 |
| title | STING protects against cardiac dysfunction and remodelling by blocking autophagy |
| title_full | STING protects against cardiac dysfunction and remodelling by blocking autophagy |
| title_fullStr | STING protects against cardiac dysfunction and remodelling by blocking autophagy |
| title_full_unstemmed | STING protects against cardiac dysfunction and remodelling by blocking autophagy |
| title_short | STING protects against cardiac dysfunction and remodelling by blocking autophagy |
| title_sort | sting protects against cardiac dysfunction and remodelling by blocking autophagy |
| topic | STING Cardiac remodelling Inflammation Autophagy ULK1 |
| url | https://doi.org/10.1186/s12964-021-00793-0 |
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