دورية أكاديمية
Dopaminylation of endothelial TPI1 suppresses ferroptotic angiocrine signals to promote lung regeneration over fibrosis.
| العنوان: | Dopaminylation of endothelial TPI1 suppresses ferroptotic angiocrine signals to promote lung regeneration over fibrosis. |
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| المؤلفون: | Mo C; Key Lab of Birth Defects and Related Diseases of Women and Children of MOE, State Key Lab of Biotherapy, State Key Laboratory of Respiratory Health and Multimorbidity, NHC Key Laboratory of Chronobiology, Sichuan-Chongqing Key Lab of Bio-Resource Research and Utilization, Development and Related Disease of Women and Children Key Lab of Sichuan, West China Second University Hospital, College of Life Sciences, Sichuan University, Chengdu, China., Li H; Key Lab of Birth Defects and Related Diseases of Women and Children of MOE, State Key Lab of Biotherapy, State Key Laboratory of Respiratory Health and Multimorbidity, NHC Key Laboratory of Chronobiology, Sichuan-Chongqing Key Lab of Bio-Resource Research and Utilization, Development and Related Disease of Women and Children Key Lab of Sichuan, West China Second University Hospital, College of Life Sciences, Sichuan University, Chengdu, China., Yan M; Key Lab of Birth Defects and Related Diseases of Women and Children of MOE, State Key Lab of Biotherapy, State Key Laboratory of Respiratory Health and Multimorbidity, NHC Key Laboratory of Chronobiology, Sichuan-Chongqing Key Lab of Bio-Resource Research and Utilization, Development and Related Disease of Women and Children Key Lab of Sichuan, West China Second University Hospital, College of Life Sciences, Sichuan University, Chengdu, China., Xu S; Key Lab of Birth Defects and Related Diseases of Women and Children of MOE, State Key Lab of Biotherapy, State Key Laboratory of Respiratory Health and Multimorbidity, NHC Key Laboratory of Chronobiology, Sichuan-Chongqing Key Lab of Bio-Resource Research and Utilization, Development and Related Disease of Women and Children Key Lab of Sichuan, West China Second University Hospital, College of Life Sciences, Sichuan University, Chengdu, China., Wu J; Key Lab of Birth Defects and Related Diseases of Women and Children of MOE, State Key Lab of Biotherapy, State Key Laboratory of Respiratory Health and Multimorbidity, NHC Key Laboratory of Chronobiology, Sichuan-Chongqing Key Lab of Bio-Resource Research and Utilization, Development and Related Disease of Women and Children Key Lab of Sichuan, West China Second University Hospital, College of Life Sciences, Sichuan University, Chengdu, China., Li J; Key Lab of Birth Defects and Related Diseases of Women and Children of MOE, State Key Lab of Biotherapy, State Key Laboratory of Respiratory Health and Multimorbidity, NHC Key Laboratory of Chronobiology, Sichuan-Chongqing Key Lab of Bio-Resource Research and Utilization, Development and Related Disease of Women and Children Key Lab of Sichuan, West China Second University Hospital, College of Life Sciences, Sichuan University, Chengdu, China., Yang X; Key Lab of Birth Defects and Related Diseases of Women and Children of MOE, State Key Lab of Biotherapy, State Key Laboratory of Respiratory Health and Multimorbidity, NHC Key Laboratory of Chronobiology, Sichuan-Chongqing Key Lab of Bio-Resource Research and Utilization, Development and Related Disease of Women and Children Key Lab of Sichuan, West China Second University Hospital, College of Life Sciences, Sichuan University, Chengdu, China., Li Y; Key Lab of Birth Defects and Related Diseases of Women and Children of MOE, State Key Lab of Biotherapy, State Key Laboratory of Respiratory Health and Multimorbidity, NHC Key Laboratory of Chronobiology, Sichuan-Chongqing Key Lab of Bio-Resource Research and Utilization, Development and Related Disease of Women and Children Key Lab of Sichuan, West China Second University Hospital, College of Life Sciences, Sichuan University, Chengdu, China., Yang J; Key Lab of Birth Defects and Related Diseases of Women and Children of MOE, State Key Lab of Biotherapy, State Key Laboratory of Respiratory Health and Multimorbidity, NHC Key Laboratory of Chronobiology, Sichuan-Chongqing Key Lab of Bio-Resource Research and Utilization, Development and Related Disease of Women and Children Key Lab of Sichuan, West China Second University Hospital, College of Life Sciences, Sichuan University, Chengdu, China., Su X; Key Lab of Birth Defects and Related Diseases of Women and Children of MOE, State Key Lab of Biotherapy, State Key Laboratory of Respiratory Health and Multimorbidity, NHC Key Laboratory of Chronobiology, Sichuan-Chongqing Key Lab of Bio-Resource Research and Utilization, Development and Related Disease of Women and Children Key Lab of Sichuan, West China Second University Hospital, College of Life Sciences, Sichuan University, Chengdu, China., Liu J; Key Lab of Birth Defects and Related Diseases of Women and Children of MOE, State Key Lab of Biotherapy, State Key Laboratory of Respiratory Health and Multimorbidity, NHC Key Laboratory of Chronobiology, Sichuan-Chongqing Key Lab of Bio-Resource Research and Utilization, Development and Related Disease of Women and Children Key Lab of Sichuan, West China Second University Hospital, College of Life Sciences, Sichuan University, Chengdu, China., Wu C; Key Lab of Birth Defects and Related Diseases of Women and Children of MOE, State Key Lab of Biotherapy, State Key Laboratory of Respiratory Health and Multimorbidity, NHC Key Laboratory of Chronobiology, Sichuan-Chongqing Key Lab of Bio-Resource Research and Utilization, Development and Related Disease of Women and Children Key Lab of Sichuan, West China Second University Hospital, College of Life Sciences, Sichuan University, Chengdu, China., Wang Y; Key Lab of Birth Defects and Related Diseases of Women and Children of MOE, State Key Lab of Biotherapy, State Key Laboratory of Respiratory Health and Multimorbidity, NHC Key Laboratory of Chronobiology, Sichuan-Chongqing Key Lab of Bio-Resource Research and Utilization, Development and Related Disease of Women and Children Key Lab of Sichuan, West China Second University Hospital, College of Life Sciences, Sichuan University, Chengdu, China., Dong H; Key Lab of Birth Defects and Related Diseases of Women and Children of MOE, State Key Lab of Biotherapy, State Key Laboratory of Respiratory Health and Multimorbidity, NHC Key Laboratory of Chronobiology, Sichuan-Chongqing Key Lab of Bio-Resource Research and Utilization, Development and Related Disease of Women and Children Key Lab of Sichuan, West China Second University Hospital, College of Life Sciences, Sichuan University, Chengdu, China., Chen L; Key Lab of Birth Defects and Related Diseases of Women and Children of MOE, State Key Lab of Biotherapy, State Key Laboratory of Respiratory Health and Multimorbidity, NHC Key Laboratory of Chronobiology, Sichuan-Chongqing Key Lab of Bio-Resource Research and Utilization, Development and Related Disease of Women and Children Key Lab of Sichuan, West China Second University Hospital, College of Life Sciences, Sichuan University, Chengdu, China., Dai L; Key Lab of Birth Defects and Related Diseases of Women and Children of MOE, State Key Lab of Biotherapy, State Key Laboratory of Respiratory Health and Multimorbidity, NHC Key Laboratory of Chronobiology, Sichuan-Chongqing Key Lab of Bio-Resource Research and Utilization, Development and Related Disease of Women and Children Key Lab of Sichuan, West China Second University Hospital, College of Life Sciences, Sichuan University, Chengdu, China., Zhang M; Department of General Surgery, Department of Thoracic Surgery and Institute of Thoracic Oncology, Laboratory of Gastrointestinal Cancer and Liver Disease, West China Hospital, Sichuan University, Chengdu, China. Electronic address: zmhxdoctor@wchscu.edu.cn., Pu Q; Department of General Surgery, Department of Thoracic Surgery and Institute of Thoracic Oncology, Laboratory of Gastrointestinal Cancer and Liver Disease, West China Hospital, Sichuan University, Chengdu, China. Electronic address: puqiang100@163.com., Yang L; Department of Pathophysiology, Harbin Medical University, Harbin, China. Electronic address: limingyang@ems.hrbmu.edu.cn., Ye T; Key Lab of Birth Defects and Related Diseases of Women and Children of MOE, State Key Lab of Biotherapy, State Key Laboratory of Respiratory Health and Multimorbidity, NHC Key Laboratory of Chronobiology, Sichuan-Chongqing Key Lab of Bio-Resource Research and Utilization, Development and Related Disease of Women and Children Key Lab of Sichuan, West China Second University Hospital, College of Life Sciences, Sichuan University, Chengdu, China; Department of General Surgery, Department of Thoracic Surgery and Institute of Thoracic Oncology, Laboratory of Gastrointestinal Cancer and Liver Disease, West China Hospital, Sichuan University, Chengdu, China. Electronic address: yeth1309@scu.edu.cn., Cao Z; Key Lab of Birth Defects and Related Diseases of Women and Children of MOE, State Key Lab of Biotherapy, State Key Laboratory of Respiratory Health and Multimorbidity, NHC Key Laboratory of Chronobiology, Sichuan-Chongqing Key Lab of Bio-Resource Research and Utilization, Development and Related Disease of Women and Children Key Lab of Sichuan, West China Second University Hospital, College of Life Sciences, Sichuan University, Chengdu, China. Electronic address: zhongweicao@scu.edu.cn., Ding BS; Key Lab of Birth Defects and Related Diseases of Women and Children of MOE, State Key Lab of Biotherapy, State Key Laboratory of Respiratory Health and Multimorbidity, NHC Key Laboratory of Chronobiology, Sichuan-Chongqing Key Lab of Bio-Resource Research and Utilization, Development and Related Disease of Women and Children Key Lab of Sichuan, West China Second University Hospital, College of Life Sciences, Sichuan University, Chengdu, China. Electronic address: dingbisen@scu.edu.cn. |
| المصدر: | Cell metabolism [Cell Metab] 2024 Aug 06; Vol. 36 (8), pp. 1839-1857.e12. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101233170 Publication Model: Print Cited Medium: Internet ISSN: 1932-7420 (Electronic) Linking ISSN: 15504131 NLM ISO Abbreviation: Cell Metab Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, Mass. : Cell Press, c2005- |
| مواضيع طبية MeSH: | Lung*/metabolism , Lung*/pathology , Ferroptosis* , Endothelial Cells*/metabolism, Animals ; Mice ; Humans ; Regeneration ; Triose-Phosphate Isomerase/metabolism ; Mice, Inbred C57BL ; Signal Transduction ; Pulmonary Fibrosis/metabolism ; Pulmonary Fibrosis/pathology ; Male |
| مستخلص: | Lungs can undergo facultative regeneration, but handicapped regeneration often leads to fibrosis. How microenvironmental cues coordinate lung regeneration via modulating cell death remains unknown. Here, we reveal that the neurotransmitter dopamine modifies the endothelial niche to suppress ferroptosis, promoting lung regeneration over fibrosis. A chemoproteomic approach shows that dopamine blocks ferroptosis in endothelial cells (ECs) via dopaminylating triosephosphate isomerase 1 (TPI1). Suppressing TPI1 dopaminylation in ECs triggers ferroptotic angiocrine signaling to aberrantly activate fibroblasts, leading to a transition from lung regeneration to fibrosis. Mechanistically, dopaminylation of glutamine (Q) 65 residue in TPI1 directionally enhances TPI1's activity to convert dihydroxyacetone phosphate (DHAP) to glyceraldehyde 3-phosphate (GAP), directing ether phospholipid synthesis to glucose metabolism in regenerating lung ECs. This metabolic shift attenuates lipid peroxidation and blocks ferroptosis. Restoring TPI1 Q65 dopaminylation in an injured endothelial niche overturns ferroptosis to normalize pro-regenerative angiocrine function and alleviate lung fibrosis. Overall, dopaminylation of TPI1 balances lipid/glucose metabolism and suppresses pro-fibrotic ferroptosis in regenerating lungs. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: angiocrine factors; dopaminylation; endothelial cells; ferroptosis; glucose metabolism; lipid metabolism; lung fibrosis; lung regeneration; vascular niche |
| المشرفين على المادة: | EC 5.3.1.1 (Triose-Phosphate Isomerase) |
| تواريخ الأحداث: | Date Created: 20240807 Date Completed: 20240807 Latest Revision: 20240807 |
| رمز التحديث: | 20240808 |
| DOI: | 10.1016/j.cmet.2024.07.008 |
| PMID: | 39111287 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1932-7420 |
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| DOI: | 10.1016/j.cmet.2024.07.008 |