LncTRPM2-AS inhibits TRIM21-mediated TRPM2 ubiquitination and prevents autophagy-induced apoptosis of macrophages in asthma
Abstract Long non-coding RNAs (lncRNAs) play a crucial role in macrophage development but little is known about their role in asthma. Here, we investigated the role of lncRNA lncTRPM2-AS in asthma and found that lncTRPM2-AS participates in the promotion of macrophage inflammation. Downregulation of...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2021-12-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-021-04437-6 |
| _version_ | 1798026843128856576 |
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| author | Xiaoping Li Wenwen Wang Yu Shao Ji Zhou Jiaqi Huang Fei Xu Xiu Gao Mengyun Wu Yongli Dong Wenyan Wu Jiamin Cai Junyao Wang Yunfei Ye Zhengrong Chen Chuangli Hao Yi Yang Jinping Zhang |
| author_facet | Xiaoping Li Wenwen Wang Yu Shao Ji Zhou Jiaqi Huang Fei Xu Xiu Gao Mengyun Wu Yongli Dong Wenyan Wu Jiamin Cai Junyao Wang Yunfei Ye Zhengrong Chen Chuangli Hao Yi Yang Jinping Zhang |
| author_sort | Xiaoping Li |
| collection | DOAJ |
| description | Abstract Long non-coding RNAs (lncRNAs) play a crucial role in macrophage development but little is known about their role in asthma. Here, we investigated the role of lncRNA lncTRPM2-AS in asthma and found that lncTRPM2-AS participates in the promotion of macrophage inflammation. Downregulation of lncTRPM2-AS promoted apoptosis and inhibited proliferation and production of cytokines including IL-1β, IL-4, IL-6, IL-10, TNF-α, and TGF-β. RNA-immunoprecipitation and mass spectrometry indicated that the protein TRPM2 interacted with both lncTRPM2-AS and the E3 ubiquitin ligase TRIM21. LncTRPM2-AS silencing enhanced the interaction between TRIM21 and TRPM2, resulting in elevated levels of ubiquitin-related degradation of TRPM2. Mutation analysis indicated that TRPM2 K1218 is a key site for TRIM21-dependent ubiquitination. Downregulation of lncTRPM2-AS significantly decreased intracellular calcium levels by restraining TRPM2 protein expression, which in turn decreased ROS levels and increased autophagy to promote macrophage apoptosis and reduce cytokine production, together inhibiting macrophage inflammation. Taken together, our findings demonstrate that lncTRPM2-AS blocks the ubiquitination of TRPM2 via TRIM21 and inhibits autophagy-induced apoptosis which may contribute to macrophage inflammation in asthma. |
| first_indexed | 2024-04-11T18:41:48Z |
| format | Article |
| id | doaj.art-38b1f0ee128a4851a66dfcd69d4b2f0a |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-11T18:41:48Z |
| publishDate | 2021-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-38b1f0ee128a4851a66dfcd69d4b2f0a2022-12-22T04:08:57ZengNature Publishing GroupCell Death and Disease2041-48892021-12-01121211010.1038/s41419-021-04437-6LncTRPM2-AS inhibits TRIM21-mediated TRPM2 ubiquitination and prevents autophagy-induced apoptosis of macrophages in asthmaXiaoping Li0Wenwen Wang1Yu Shao2Ji Zhou3Jiaqi Huang4Fei Xu5Xiu Gao6Mengyun Wu7Yongli Dong8Wenyan Wu9Jiamin Cai10Junyao Wang11Yunfei Ye12Zhengrong Chen13Chuangli Hao14Yi Yang15Jinping Zhang16Institutes of Biology and Medical Sciences, Soochow UniversityInstitutes of Biology and Medical Sciences, Soochow UniversityInstitutes of Biology and Medical Sciences, Soochow UniversityInstitutes of Biology and Medical Sciences, Soochow UniversityDepartment of Respiratory Medicine, Children’s Hospital of Soochow UniversityInstitutes of Biology and Medical Sciences, Soochow UniversityInstitutes of Biology and Medical Sciences, Soochow UniversityInstitutes of Biology and Medical Sciences, Soochow UniversityInstitutes of Biology and Medical Sciences, Soochow UniversityInstitutes of Biology and Medical Sciences, Soochow UniversityInstitutes of Biology and Medical Sciences, Soochow UniversityInstitutes of Biology and Medical Sciences, Soochow UniversityInstitutes of Biology and Medical Sciences, Soochow UniversityDepartment of Respiratory Medicine, Children’s Hospital of Soochow UniversityDepartment of Respiratory Medicine, Children’s Hospital of Soochow UniversityInstitutes of Biology and Medical Sciences, Soochow UniversityInstitutes of Biology and Medical Sciences, Soochow UniversityAbstract Long non-coding RNAs (lncRNAs) play a crucial role in macrophage development but little is known about their role in asthma. Here, we investigated the role of lncRNA lncTRPM2-AS in asthma and found that lncTRPM2-AS participates in the promotion of macrophage inflammation. Downregulation of lncTRPM2-AS promoted apoptosis and inhibited proliferation and production of cytokines including IL-1β, IL-4, IL-6, IL-10, TNF-α, and TGF-β. RNA-immunoprecipitation and mass spectrometry indicated that the protein TRPM2 interacted with both lncTRPM2-AS and the E3 ubiquitin ligase TRIM21. LncTRPM2-AS silencing enhanced the interaction between TRIM21 and TRPM2, resulting in elevated levels of ubiquitin-related degradation of TRPM2. Mutation analysis indicated that TRPM2 K1218 is a key site for TRIM21-dependent ubiquitination. Downregulation of lncTRPM2-AS significantly decreased intracellular calcium levels by restraining TRPM2 protein expression, which in turn decreased ROS levels and increased autophagy to promote macrophage apoptosis and reduce cytokine production, together inhibiting macrophage inflammation. Taken together, our findings demonstrate that lncTRPM2-AS blocks the ubiquitination of TRPM2 via TRIM21 and inhibits autophagy-induced apoptosis which may contribute to macrophage inflammation in asthma.https://doi.org/10.1038/s41419-021-04437-6 |
| spellingShingle | Xiaoping Li Wenwen Wang Yu Shao Ji Zhou Jiaqi Huang Fei Xu Xiu Gao Mengyun Wu Yongli Dong Wenyan Wu Jiamin Cai Junyao Wang Yunfei Ye Zhengrong Chen Chuangli Hao Yi Yang Jinping Zhang LncTRPM2-AS inhibits TRIM21-mediated TRPM2 ubiquitination and prevents autophagy-induced apoptosis of macrophages in asthma Cell Death and Disease |
| title | LncTRPM2-AS inhibits TRIM21-mediated TRPM2 ubiquitination and prevents autophagy-induced apoptosis of macrophages in asthma |
| title_full | LncTRPM2-AS inhibits TRIM21-mediated TRPM2 ubiquitination and prevents autophagy-induced apoptosis of macrophages in asthma |
| title_fullStr | LncTRPM2-AS inhibits TRIM21-mediated TRPM2 ubiquitination and prevents autophagy-induced apoptosis of macrophages in asthma |
| title_full_unstemmed | LncTRPM2-AS inhibits TRIM21-mediated TRPM2 ubiquitination and prevents autophagy-induced apoptosis of macrophages in asthma |
| title_short | LncTRPM2-AS inhibits TRIM21-mediated TRPM2 ubiquitination and prevents autophagy-induced apoptosis of macrophages in asthma |
| title_sort | lnctrpm2 as inhibits trim21 mediated trpm2 ubiquitination and prevents autophagy induced apoptosis of macrophages in asthma |
| url | https://doi.org/10.1038/s41419-021-04437-6 |
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