Arginine methyltransferase PRMT1 promotes ferroptosis through EGR1/GLS2 axis in sepsis-related acute lung injury
Abstract Acute lung injury (ALI), a frequent and severe complication of sepsis, is associated with significant mortality rates. Previous studies indicated that GLS2 plays a key role in promoting ferroptosis. However, its underlying mechanisms remain unclear. Here we show, there were elevated ferropt...
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| Format: | Article |
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Nature Portfolio
2025-02-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07531-z |
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| author | Min Li Longhui Hu Qiao Ke Zhao Li Chujun Ruan Hanjing Lu Xiaoran Liu |
| author_facet | Min Li Longhui Hu Qiao Ke Zhao Li Chujun Ruan Hanjing Lu Xiaoran Liu |
| author_sort | Min Li |
| collection | DOAJ |
| description | Abstract Acute lung injury (ALI), a frequent and severe complication of sepsis, is associated with significant mortality rates. Previous studies indicated that GLS2 plays a key role in promoting ferroptosis. However, its underlying mechanisms remain unclear. Here we show, there were elevated ferroptosis and increased expression levels of protein arginine methyltransferase 1 (PRMT1), early growth response 1 (EGR1), and glutaminase 2 (GLS2) in both in vitro and in vivo ALI models. Additionally, EGR1 was found to induce the transcription of GLS2, thereby promoting ferroptosis. We also discovered that the protein level of EGR1 was increased through enhanced stability, facilitated by PRMT1-mediated arginine methylation, and reduced ubiquitination degradation regulated by neural precursor cell expressed developmentally down-regulated protein 4 like (NEDD4L). The in vivo results confirmed that the knockdown of PRMT1 suppressed ferroptosis via the EGR1/GLS2 axis. Our findings suggest that PRMT1-mediated stabilization of EGR1 promoted sepsis induced ALI via GLS2, highlighting the therapeutic potential of targeting PRMT1 or EGR1 in the treatment of sepsis-induced ALI. |
| format | Article |
| id | doaj-art-21448ada047e4e068530141e5ea3be60 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-21448ada047e4e068530141e5ea3be602025-02-09T12:50:35ZengNature PortfolioCommunications Biology2399-36422025-02-018111510.1038/s42003-025-07531-zArginine methyltransferase PRMT1 promotes ferroptosis through EGR1/GLS2 axis in sepsis-related acute lung injuryMin Li0Longhui Hu1Qiao Ke2Zhao Li3Chujun Ruan4Hanjing Lu5Xiaoran Liu6Emergency trauma College of Hainan Medical UniversityEmergency Department, Hainan Affiliated Hospital of Hainan Medical University (Hainan General Hospital)Emergency Department, Hainan Affiliated Hospital of Hainan Medical University (Hainan General Hospital)Emergency trauma College of Hainan Medical UniversityEmergency Department, Hainan Affiliated Hospital of Hainan Medical University (Hainan General Hospital)Emergency trauma College of Hainan Medical UniversityEmergency trauma College of Hainan Medical UniversityAbstract Acute lung injury (ALI), a frequent and severe complication of sepsis, is associated with significant mortality rates. Previous studies indicated that GLS2 plays a key role in promoting ferroptosis. However, its underlying mechanisms remain unclear. Here we show, there were elevated ferroptosis and increased expression levels of protein arginine methyltransferase 1 (PRMT1), early growth response 1 (EGR1), and glutaminase 2 (GLS2) in both in vitro and in vivo ALI models. Additionally, EGR1 was found to induce the transcription of GLS2, thereby promoting ferroptosis. We also discovered that the protein level of EGR1 was increased through enhanced stability, facilitated by PRMT1-mediated arginine methylation, and reduced ubiquitination degradation regulated by neural precursor cell expressed developmentally down-regulated protein 4 like (NEDD4L). The in vivo results confirmed that the knockdown of PRMT1 suppressed ferroptosis via the EGR1/GLS2 axis. Our findings suggest that PRMT1-mediated stabilization of EGR1 promoted sepsis induced ALI via GLS2, highlighting the therapeutic potential of targeting PRMT1 or EGR1 in the treatment of sepsis-induced ALI.https://doi.org/10.1038/s42003-025-07531-z |
| spellingShingle | Min Li Longhui Hu Qiao Ke Zhao Li Chujun Ruan Hanjing Lu Xiaoran Liu Arginine methyltransferase PRMT1 promotes ferroptosis through EGR1/GLS2 axis in sepsis-related acute lung injury Communications Biology |
| title | Arginine methyltransferase PRMT1 promotes ferroptosis through EGR1/GLS2 axis in sepsis-related acute lung injury |
| title_full | Arginine methyltransferase PRMT1 promotes ferroptosis through EGR1/GLS2 axis in sepsis-related acute lung injury |
| title_fullStr | Arginine methyltransferase PRMT1 promotes ferroptosis through EGR1/GLS2 axis in sepsis-related acute lung injury |
| title_full_unstemmed | Arginine methyltransferase PRMT1 promotes ferroptosis through EGR1/GLS2 axis in sepsis-related acute lung injury |
| title_short | Arginine methyltransferase PRMT1 promotes ferroptosis through EGR1/GLS2 axis in sepsis-related acute lung injury |
| title_sort | arginine methyltransferase prmt1 promotes ferroptosis through egr1 gls2 axis in sepsis related acute lung injury |
| url | https://doi.org/10.1038/s42003-025-07531-z |
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