Meteorin-like/Meteorin-β protects LPS-induced acute lung injury by activating SIRT1-P53-SLC7A11 mediated ferroptosis pathway
Abstract Background Ferroptosis plays an essential role in lipopolysaccharide (LPS)-induced acute lung injury (ALI). Meteorin-like/Meteorin-β (Metrnβ) is a protein secreted by skeletal muscle and adipose tissue and plays a role in cardiovascular diseases. However, its role in acute lung injury has n...
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BMC
2023-10-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-023-00714-6 |
| _version_ | 1827633924448190464 |
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| author | Zhen Chen Jun Li Huan Peng Mengli Zhang Xian Wu Feng Gui Wei Li Fen Ai Bo Yu Yijue Liu |
| author_facet | Zhen Chen Jun Li Huan Peng Mengli Zhang Xian Wu Feng Gui Wei Li Fen Ai Bo Yu Yijue Liu |
| author_sort | Zhen Chen |
| collection | DOAJ |
| description | Abstract Background Ferroptosis plays an essential role in lipopolysaccharide (LPS)-induced acute lung injury (ALI). Meteorin-like/Meteorin-β (Metrnβ) is a protein secreted by skeletal muscle and adipose tissue and plays a role in cardiovascular diseases. However, its role in acute lung injury has not been elucidated. Methods In this study, we used an adenovirus (Ad) delivery system to overexpress or knockdown Metrnβ in lung tissue to examine the role of Metrnβ in LPS-induced acute lung injury. Results We found that ferroptosis was increased during LPS-induced ALI. The expression of Metrnβ was reduced in ALI lung tissue. Overexpression of Metrnβ in lung tissue alleviated LPS-induced lung injury, inflammation, and ferroptosis. Moreover, Metrnβ knockout in lung tissue accelerated LPS-induced ALI, inflammation, and ferroptosis. We also cultured MLE-12 cells and transfected the cells with Ad-Metrnβ or Metrnβ siRNA. Metrnβ overexpression ameliorated LPS-induced MLE cell death, inflammation and ferroptosis, while Metrnβ knockdown aggregated cell survival and decreased inflammation and ferroptosis. Moreover, we found that Metrnβ enhanced ferroptosis-related Gpx4 expression and reduced ferroportin and ferritin levels. Furthermore, we found that Metrnβ positively regulated SIRT1 transcription thus inhibited P53, increased SLC7A11 expression. When we used the ferroptosis inhibitor ferrostatin-1, the deteriorating effects of Metrnβ knockout were abolished in ALI mice. Moreover, SIRT1 knockout also abolished the protective effects of Metrnβ overexpression in vivo. Conclusions Taken together, Metrnβ could protect LPS-induced ALI by activating SIRT1-P53- SLC7A11 mediated ferroptosis inhibition. |
| first_indexed | 2024-03-09T15:06:17Z |
| format | Article |
| id | doaj.art-c3d5bcd8b0404e60a9d5cdb61dcb3059 |
| institution | Directory Open Access Journal |
| issn | 1528-3658 |
| language | English |
| last_indexed | 2024-03-09T15:06:17Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj.art-c3d5bcd8b0404e60a9d5cdb61dcb30592023-11-26T13:39:28ZengBMCMolecular Medicine1528-36582023-10-0129111510.1186/s10020-023-00714-6Meteorin-like/Meteorin-β protects LPS-induced acute lung injury by activating SIRT1-P53-SLC7A11 mediated ferroptosis pathwayZhen Chen0Jun Li1Huan Peng2Mengli Zhang3Xian Wu4Feng Gui5Wei Li6Fen Ai7Bo Yu8Yijue Liu9Department of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Critical Care Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background Ferroptosis plays an essential role in lipopolysaccharide (LPS)-induced acute lung injury (ALI). Meteorin-like/Meteorin-β (Metrnβ) is a protein secreted by skeletal muscle and adipose tissue and plays a role in cardiovascular diseases. However, its role in acute lung injury has not been elucidated. Methods In this study, we used an adenovirus (Ad) delivery system to overexpress or knockdown Metrnβ in lung tissue to examine the role of Metrnβ in LPS-induced acute lung injury. Results We found that ferroptosis was increased during LPS-induced ALI. The expression of Metrnβ was reduced in ALI lung tissue. Overexpression of Metrnβ in lung tissue alleviated LPS-induced lung injury, inflammation, and ferroptosis. Moreover, Metrnβ knockout in lung tissue accelerated LPS-induced ALI, inflammation, and ferroptosis. We also cultured MLE-12 cells and transfected the cells with Ad-Metrnβ or Metrnβ siRNA. Metrnβ overexpression ameliorated LPS-induced MLE cell death, inflammation and ferroptosis, while Metrnβ knockdown aggregated cell survival and decreased inflammation and ferroptosis. Moreover, we found that Metrnβ enhanced ferroptosis-related Gpx4 expression and reduced ferroportin and ferritin levels. Furthermore, we found that Metrnβ positively regulated SIRT1 transcription thus inhibited P53, increased SLC7A11 expression. When we used the ferroptosis inhibitor ferrostatin-1, the deteriorating effects of Metrnβ knockout were abolished in ALI mice. Moreover, SIRT1 knockout also abolished the protective effects of Metrnβ overexpression in vivo. Conclusions Taken together, Metrnβ could protect LPS-induced ALI by activating SIRT1-P53- SLC7A11 mediated ferroptosis inhibition.https://doi.org/10.1186/s10020-023-00714-6MetrnβAcute lung injurySIRT1FerroptosisSLC7A11 |
| spellingShingle | Zhen Chen Jun Li Huan Peng Mengli Zhang Xian Wu Feng Gui Wei Li Fen Ai Bo Yu Yijue Liu Meteorin-like/Meteorin-β protects LPS-induced acute lung injury by activating SIRT1-P53-SLC7A11 mediated ferroptosis pathway Molecular Medicine Metrnβ Acute lung injury SIRT1 Ferroptosis SLC7A11 |
| title | Meteorin-like/Meteorin-β protects LPS-induced acute lung injury by activating SIRT1-P53-SLC7A11 mediated ferroptosis pathway |
| title_full | Meteorin-like/Meteorin-β protects LPS-induced acute lung injury by activating SIRT1-P53-SLC7A11 mediated ferroptosis pathway |
| title_fullStr | Meteorin-like/Meteorin-β protects LPS-induced acute lung injury by activating SIRT1-P53-SLC7A11 mediated ferroptosis pathway |
| title_full_unstemmed | Meteorin-like/Meteorin-β protects LPS-induced acute lung injury by activating SIRT1-P53-SLC7A11 mediated ferroptosis pathway |
| title_short | Meteorin-like/Meteorin-β protects LPS-induced acute lung injury by activating SIRT1-P53-SLC7A11 mediated ferroptosis pathway |
| title_sort | meteorin like meteorin β protects lps induced acute lung injury by activating sirt1 p53 slc7a11 mediated ferroptosis pathway |
| topic | Metrnβ Acute lung injury SIRT1 Ferroptosis SLC7A11 |
| url | https://doi.org/10.1186/s10020-023-00714-6 |
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