دورية أكاديمية
Apoptotic Vesicular Metabolism Contributes to Organelle Assembly and Safeguards Liver Homeostasis and Regeneration.
| العنوان: | Apoptotic Vesicular Metabolism Contributes to Organelle Assembly and Safeguards Liver Homeostasis and Regeneration. |
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| المؤلفون: | Sui B; State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Research and Development Center for Tissue Engineering, The Fourth Military Medical University, Xi'an, Shaanxi, China; Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, Pennsylvania., Wang R; Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, Pennsylvania., Chen C; Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, Pennsylvania., Kou X; Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, Pennsylvania; Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, South China Center of Craniofacial Stem Cell Research, Guangzhou, China., Wu D; Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, South China Center of Craniofacial Stem Cell Research, Guangzhou, China., Fu Y; Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, South China Center of Craniofacial Stem Cell Research, Guangzhou, China., Lei F; Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, South China Center of Craniofacial Stem Cell Research, Guangzhou, China., Wang Y; Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, Michigan., Liu Y; Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, Hubei, China., Chen X; Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore, Singapore; Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Nanomedicine Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A∗STAR), Singapore, Singapore., Xu H; Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, The Fourth Military Medical University, Xi'an, Shaanxi, China., Liu Y; Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, The Fourth Military Medical University, Xi'an, Shaanxi, China., Kang J; Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, The Fourth Military Medical University, Xi'an, Shaanxi, China., Liu H; Department of Chemical and Biological Engineering, Department of Chemistry, The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction and Institute for Advanced Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China., Kwok RTK; Department of Chemical and Biological Engineering, Department of Chemistry, The Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction and Institute for Advanced Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China., Tang BZ; Shenzhen Institute of Aggregate Science and Technology, School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen, Guangdong, China., Yan H; Department of Anesthesiology and Critical Care Medicine, Renji Hospital, Jiaotong University School of Medicine, Shanghai, China., Wang M; Department of Cell Biology, Center for Stem Cell and Medicine, The Second Military Medical University, Shanghai, China., Xiang L; Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, South China Center of Craniofacial Stem Cell Research, Guangzhou, China., Yan X; Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, South China Center of Craniofacial Stem Cell Research, Guangzhou, China., Zhang X; Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, Pennsylvania., Ma L; Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, Pennsylvania; Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, South China Center of Craniofacial Stem Cell Research, Guangzhou, China., Shi S; Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, Pennsylvania; Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, South China Center of Craniofacial Stem Cell Research, Guangzhou, China. Electronic address: songtaos@upenn.edu., Jin Y; State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Research and Development Center for Tissue Engineering, The Fourth Military Medical University, Xi'an, Shaanxi, China. Electronic address: yanjin@fmmu.edu.cn. |
| المصدر: | Gastroenterology [Gastroenterology] 2024 Jul; Vol. 167 (2), pp. 343-356. Date of Electronic Publication: 2024 Feb 10. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: W.B. Saunders Country of Publication: United States NLM ID: 0374630 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-0012 (Electronic) Linking ISSN: 00165085 NLM ISO Abbreviation: Gastroenterology Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Philadelphia, PA : W.B. Saunders Original Publication: Baltimore. |
| مواضيع طبية MeSH: | Liver Regeneration* , Apoptosis* , Hepatocytes*/metabolism , Hepatocytes*/pathology , Liver*/metabolism , Liver*/pathology , Homeostasis* , Mice, Knockout*, Animals ; Caspase 3/metabolism ; Mice ; Hepatectomy ; Disease Models, Animal ; fas Receptor/metabolism ; fas Receptor/genetics ; Golgi Apparatus/metabolism ; Endocytosis ; Chemical and Drug Induced Liver Injury/pathology ; Chemical and Drug Induced Liver Injury/metabolism ; Chemical and Drug Induced Liver Injury/etiology ; Chemical and Drug Induced Liver Injury/genetics ; Mice, Inbred C57BL ; Acetaminophen ; Male |
| مستخلص: | Background & Aims: Apoptosis generates plenty of membrane-bound nanovesicles, the apoptotic vesicles (apoVs), which show promise for biomedical applications. The liver serves as a significant organ for apoptotic material removal. Whether and how the liver metabolizes apoptotic vesicular products and contributes to liver health and disease is unrecognized. Methods: apoVs were labeled and traced after intravenous infusion. Apoptosis-deficient mice by Fas mutant (Fas mut ) and Caspase-3 knockout (Casp3 -/- ) were used with apoV replenishment to evaluate the physiological apoV function. Combinations of morphologic, biochemical, cellular, and molecular assays were applied to assess the liver while hepatocyte analysis was performed. Partial hepatectomy and acetaminophen liver failure models were established to investigate liver regeneration and disease recovery. Results: We discovered that the liver is a major metabolic organ of circulatory apoVs, in which apoVs undergo endocytosis by hepatocytes via a sugar recognition system. Moreover, apoVs play an indispensable role to counteract hepatocellular injury and liver impairment in apoptosis-deficient mice upon replenishment. Surprisingly, apoVs form a chimeric organelle complex with the hepatocyte Golgi apparatus through the soluble N-ethylmaleimide-sensitive factor attachment protein receptor machinery, which preserves Golgi integrity, promotes microtubule acetylation by regulating α-tubulin N-acetyltransferase 1, and consequently facilitates hepatocyte cytokinesis for liver recovery. The assembly of the apoV-Golgi complex is further revealed to contribute to liver homeostasis, regeneration, and protection against acute liver failure. Conclusions: These findings establish a previously unrecognized functional and mechanistic framework that apoptosis through vesicular metabolism safeguards liver homeostasis and regeneration, which holds promise for hepatic disease therapeutics. (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Apoptosis; Extracellular Vesicles; Golgi Apparatus; Liver Regeneration; Nanotherapeutics |
| المشرفين على المادة: | EC 3.4.22.- (Caspase 3) 0 (fas Receptor) 0 (Fas protein, mouse) EC 3.4.22.- (Casp3 protein, mouse) 362O9ITL9D (Acetaminophen) |
| تواريخ الأحداث: | Date Created: 20240211 Date Completed: 20240622 Latest Revision: 20240622 |
| رمز التحديث: | 20240623 |
| DOI: | 10.1053/j.gastro.2024.02.001 |
| PMID: | 38342194 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 1528-0012 |
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| DOI: | 10.1053/j.gastro.2024.02.001 |