Organelle Crosstalk Regulators Are Regulated in Diseases, Tumors, and Regulatory T Cells: Novel Classification of Organelle Crosstalk Regulators
To examine whether the expressions of 260 organelle crosstalk regulators (OCRGs) in 16 functional groups are modulated in 23 diseases and 28 tumors, we performed extensive -omics data mining analyses and made a set of significant findings: (1) the ratios of upregulated vs. downregulated OCRGs are 1:...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-07-01
|
| Series: | Frontiers in Cardiovascular Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2021.713170/full |
| _version_ | 1818656098362589184 |
|---|---|
| author | Ming Liu Ming Liu Na Wu Keman Xu Fatma Saaoud Eleni Vasilopoulos Ying Shao Ruijing Zhang Ruijing Zhang Jirong Wang Jirong Wang Haitao Shen William Y. Yang Yifan Lu Yu Sun Charles Drummer Lu Liu Li Li Wenhui Hu Jun Yu Domenico Praticò Jianxin Sun Xiaohua Jiang Xiaohua Jiang Hong Wang Xiaofeng Yang Xiaofeng Yang |
| author_facet | Ming Liu Ming Liu Na Wu Keman Xu Fatma Saaoud Eleni Vasilopoulos Ying Shao Ruijing Zhang Ruijing Zhang Jirong Wang Jirong Wang Haitao Shen William Y. Yang Yifan Lu Yu Sun Charles Drummer Lu Liu Li Li Wenhui Hu Jun Yu Domenico Praticò Jianxin Sun Xiaohua Jiang Xiaohua Jiang Hong Wang Xiaofeng Yang Xiaofeng Yang |
| author_sort | Ming Liu |
| collection | DOAJ |
| description | To examine whether the expressions of 260 organelle crosstalk regulators (OCRGs) in 16 functional groups are modulated in 23 diseases and 28 tumors, we performed extensive -omics data mining analyses and made a set of significant findings: (1) the ratios of upregulated vs. downregulated OCRGs are 1:2.8 in acute inflammations, 1:1 in metabolic diseases, 1:1.2 in autoimmune diseases, and 1:3.8 in organ failures; (2) sepsis and trauma-upregulated OCRG groups such as vesicle, mitochondrial (MT) fission, and mitophagy but not others, are termed as the cell crisis-handling OCRGs. Similarly, sepsis and trauma plus organ failures upregulated seven OCRG groups including vesicle, MT fission, mitophagy, sarcoplasmic reticulum–MT, MT fusion, autophagosome–lysosome fusion, and autophagosome/endosome–lysosome fusion, classified as the cell failure-handling OCRGs; (3) suppression of autophagosome–lysosome fusion in endothelial and epithelial cells is required for viral replications, which classify this decreased group as the viral replication-suppressed OCRGs; (4) pro-atherogenic damage-associated molecular patterns (DAMPs) such as oxidized low-density lipoprotein (oxLDL), lipopolysaccharide (LPS), oxidized-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (oxPAPC), and interferons (IFNs) totally upregulated 33 OCRGs in endothelial cells (ECs) including vesicle, MT fission, mitophagy, MT fusion, endoplasmic reticulum (ER)–MT contact, ER– plasma membrane (PM) junction, autophagosome/endosome–lysosome fusion, sarcoplasmic reticulum–MT, autophagosome–endosome/lysosome fusion, and ER–Golgi complex (GC) interaction as the 10 EC-activation/inflammation-promoting OCRG groups; (5) the expression of OCRGs is upregulated more than downregulated in regulatory T cells (Tregs) from the lymph nodes, spleen, peripheral blood, intestine, and brown adipose tissue in comparison with that of CD4+CD25− T effector controls; (6) toll-like receptors (TLRs), reactive oxygen species (ROS) regulator nuclear factor erythroid 2-related factor 2 (Nrf2), and inflammasome-activated regulator caspase-1 regulated the expressions of OCRGs in diseases, virus-infected cells, and pro-atherogenic DAMP-treated ECs; (7) OCRG expressions are significantly modulated in all the 28 cancer datasets, and the upregulated OCRGs are correlated with tumor immune infiltrates in some tumors; (8) tumor promoter factor IKK2 and tumor suppressor Tp53 significantly modulate the expressions of OCRGs. Our findings provide novel insights on the roles of upregulated OCRGs in the pathogenesis of inflammatory diseases and cancers, and novel pathways for the future therapeutic interventions for inflammations, sepsis, trauma, organ failures, autoimmune diseases, metabolic cardiovascular diseases (CVDs), and cancers. |
| first_indexed | 2024-12-17T03:20:11Z |
| format | Article |
| id | doaj.art-479a440132ef4b08b0e6260a996061ca |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-17T03:20:11Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-479a440132ef4b08b0e6260a996061ca2022-12-21T22:05:32ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2021-07-01810.3389/fcvm.2021.713170713170Organelle Crosstalk Regulators Are Regulated in Diseases, Tumors, and Regulatory T Cells: Novel Classification of Organelle Crosstalk RegulatorsMing Liu0Ming Liu1Na Wu2Keman Xu3Fatma Saaoud4Eleni Vasilopoulos5Ying Shao6Ruijing Zhang7Ruijing Zhang8Jirong Wang9Jirong Wang10Haitao Shen11William Y. Yang12Yifan Lu13Yu Sun14Charles Drummer15Lu Liu16Li Li17Wenhui Hu18Jun Yu19Domenico Praticò20Jianxin Sun21Xiaohua Jiang22Xiaohua Jiang23Hong Wang24Xiaofeng Yang25Xiaofeng Yang26Centers for Cardiovascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesDepartment of Cell Biology and Genetics, School of Basic Medical Science, Shanxi Medical University, Taiyuan, ChinaDepartments of Endocrinology and Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, ChinaCenters for Cardiovascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesCenters for Cardiovascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesCenters for Cardiovascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesCenters for Cardiovascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesCenters for Cardiovascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesDepartment of Nephrology, The Affiliated People's Hospital of Shanxi Medical University, Taiyuan, ChinaCenters for Cardiovascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesDepartment of Cardiology, The Affiliated People's Hospital of Shanxi Medical University, Taiyuan, ChinaDepartments of Endocrinology and Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, ChinaRutgers University, New Brunswick, NJ, United StatesCenters for Cardiovascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesCenters for Cardiovascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesCenters for Cardiovascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesMetabolic Disease Research, Inflammation, Translational & Clinical Lung Research, Thrombosis Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesDepartment of Cell Biology and Genetics, School of Basic Medical Science, Shanxi Medical University, Taiyuan, ChinaMetabolic Disease Research, Inflammation, Translational & Clinical Lung Research, Thrombosis Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesMetabolic Disease Research, Inflammation, Translational & Clinical Lung Research, Thrombosis Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesAlzheimer's Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesDepartment of Medicine, Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA, United StatesCenters for Cardiovascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesMetabolic Disease Research, Inflammation, Translational & Clinical Lung Research, Thrombosis Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesMetabolic Disease Research, Inflammation, Translational & Clinical Lung Research, Thrombosis Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesCenters for Cardiovascular Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesMetabolic Disease Research, Inflammation, Translational & Clinical Lung Research, Thrombosis Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United StatesTo examine whether the expressions of 260 organelle crosstalk regulators (OCRGs) in 16 functional groups are modulated in 23 diseases and 28 tumors, we performed extensive -omics data mining analyses and made a set of significant findings: (1) the ratios of upregulated vs. downregulated OCRGs are 1:2.8 in acute inflammations, 1:1 in metabolic diseases, 1:1.2 in autoimmune diseases, and 1:3.8 in organ failures; (2) sepsis and trauma-upregulated OCRG groups such as vesicle, mitochondrial (MT) fission, and mitophagy but not others, are termed as the cell crisis-handling OCRGs. Similarly, sepsis and trauma plus organ failures upregulated seven OCRG groups including vesicle, MT fission, mitophagy, sarcoplasmic reticulum–MT, MT fusion, autophagosome–lysosome fusion, and autophagosome/endosome–lysosome fusion, classified as the cell failure-handling OCRGs; (3) suppression of autophagosome–lysosome fusion in endothelial and epithelial cells is required for viral replications, which classify this decreased group as the viral replication-suppressed OCRGs; (4) pro-atherogenic damage-associated molecular patterns (DAMPs) such as oxidized low-density lipoprotein (oxLDL), lipopolysaccharide (LPS), oxidized-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (oxPAPC), and interferons (IFNs) totally upregulated 33 OCRGs in endothelial cells (ECs) including vesicle, MT fission, mitophagy, MT fusion, endoplasmic reticulum (ER)–MT contact, ER– plasma membrane (PM) junction, autophagosome/endosome–lysosome fusion, sarcoplasmic reticulum–MT, autophagosome–endosome/lysosome fusion, and ER–Golgi complex (GC) interaction as the 10 EC-activation/inflammation-promoting OCRG groups; (5) the expression of OCRGs is upregulated more than downregulated in regulatory T cells (Tregs) from the lymph nodes, spleen, peripheral blood, intestine, and brown adipose tissue in comparison with that of CD4+CD25− T effector controls; (6) toll-like receptors (TLRs), reactive oxygen species (ROS) regulator nuclear factor erythroid 2-related factor 2 (Nrf2), and inflammasome-activated regulator caspase-1 regulated the expressions of OCRGs in diseases, virus-infected cells, and pro-atherogenic DAMP-treated ECs; (7) OCRG expressions are significantly modulated in all the 28 cancer datasets, and the upregulated OCRGs are correlated with tumor immune infiltrates in some tumors; (8) tumor promoter factor IKK2 and tumor suppressor Tp53 significantly modulate the expressions of OCRGs. Our findings provide novel insights on the roles of upregulated OCRGs in the pathogenesis of inflammatory diseases and cancers, and novel pathways for the future therapeutic interventions for inflammations, sepsis, trauma, organ failures, autoimmune diseases, metabolic cardiovascular diseases (CVDs), and cancers.https://www.frontiersin.org/articles/10.3389/fcvm.2021.713170/fullorganelle crosstalkinflammationcancers and tumorsviral infectionsendothelial cell activationTreg |
| spellingShingle | Ming Liu Ming Liu Na Wu Keman Xu Fatma Saaoud Eleni Vasilopoulos Ying Shao Ruijing Zhang Ruijing Zhang Jirong Wang Jirong Wang Haitao Shen William Y. Yang Yifan Lu Yu Sun Charles Drummer Lu Liu Li Li Wenhui Hu Jun Yu Domenico Praticò Jianxin Sun Xiaohua Jiang Xiaohua Jiang Hong Wang Xiaofeng Yang Xiaofeng Yang Organelle Crosstalk Regulators Are Regulated in Diseases, Tumors, and Regulatory T Cells: Novel Classification of Organelle Crosstalk Regulators Frontiers in Cardiovascular Medicine organelle crosstalk inflammation cancers and tumors viral infections endothelial cell activation Treg |
| title | Organelle Crosstalk Regulators Are Regulated in Diseases, Tumors, and Regulatory T Cells: Novel Classification of Organelle Crosstalk Regulators |
| title_full | Organelle Crosstalk Regulators Are Regulated in Diseases, Tumors, and Regulatory T Cells: Novel Classification of Organelle Crosstalk Regulators |
| title_fullStr | Organelle Crosstalk Regulators Are Regulated in Diseases, Tumors, and Regulatory T Cells: Novel Classification of Organelle Crosstalk Regulators |
| title_full_unstemmed | Organelle Crosstalk Regulators Are Regulated in Diseases, Tumors, and Regulatory T Cells: Novel Classification of Organelle Crosstalk Regulators |
| title_short | Organelle Crosstalk Regulators Are Regulated in Diseases, Tumors, and Regulatory T Cells: Novel Classification of Organelle Crosstalk Regulators |
| title_sort | organelle crosstalk regulators are regulated in diseases tumors and regulatory t cells novel classification of organelle crosstalk regulators |
| topic | organelle crosstalk inflammation cancers and tumors viral infections endothelial cell activation Treg |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2021.713170/full |
| work_keys_str_mv | AT mingliu organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT mingliu organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT nawu organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT kemanxu organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT fatmasaaoud organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT elenivasilopoulos organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT yingshao organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT ruijingzhang organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT ruijingzhang organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT jirongwang organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT jirongwang organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT haitaoshen organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT williamyyang organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT yifanlu organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT yusun organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT charlesdrummer organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT luliu organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT lili organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT wenhuihu organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT junyu organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT domenicopratico organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT jianxinsun organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT xiaohuajiang organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT xiaohuajiang organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT hongwang organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT xiaofengyang organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators AT xiaofengyang organellecrosstalkregulatorsareregulatedindiseasestumorsandregulatorytcellsnovelclassificationoforganellecrosstalkregulators |