MX1 and UBE2L6 are potential metaflammation gene targets in both diabetes and atherosclerosis
Background The coexistence of diabetes mellitus (DM) and atherosclerosis (AS) is widespread, although the explicit metabolism and metabolism-associated molecular patterns (MAMPs) responsible for the correlation are still unclear. Methods Twenty-four genetically wild-type male Ba-Ma mini pigs were ra...
| Main Authors: | , , , , , , , , , , , , , |
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PeerJ Inc.
2024-02-01
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| Online Access: | https://peerj.com/articles/16975.pdf |
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| author | Guisheng Wang Rongrong Hua Xiaoxia Chen Xucheng He Yao Dingming Hua Chen Buhuan Zhang Yuru Dong Muqing Liu Jiaxiong Liu Ting Liu Jingwei Zhao Yu Qiong Zhao Li Qiao |
| author_facet | Guisheng Wang Rongrong Hua Xiaoxia Chen Xucheng He Yao Dingming Hua Chen Buhuan Zhang Yuru Dong Muqing Liu Jiaxiong Liu Ting Liu Jingwei Zhao Yu Qiong Zhao Li Qiao |
| author_sort | Guisheng Wang |
| collection | DOAJ |
| description | Background The coexistence of diabetes mellitus (DM) and atherosclerosis (AS) is widespread, although the explicit metabolism and metabolism-associated molecular patterns (MAMPs) responsible for the correlation are still unclear. Methods Twenty-four genetically wild-type male Ba-Ma mini pigs were randomly divided into five groups distinguished by different combinations of 90 mg/kg streptozotocin (STZ) intravenous injection and high-cholesterol/lipid (HC) or high-lipid (HL) diet feeding for 9 months in total. Pigs in the STZ+HC and STZ+HL groups were injected with STZ first and then fed the HC or HL diet for 9 months. In contrast, pigs in the HC+STZ and HL+STZ groups were fed the HC or HL diet for 9 months and injected with STZ at 3 months. The controls were only fed a regular diet for 9 months. The blood glucose and abdominal aortic plaque observed through oil red O staining were used as evaluation indicators for successful modelling of DM and AS. A microarray gene expression analysis of all subjects was performed. Results Atherosclerotic lesions were observed only in the HC+STZ and STZ+HC groups. A total of 103 differentially expressed genes (DEGs) were identified as common between them. The most significantly enriched pathways of 103 common DEGs were influenza A, hepatitis C, and measles. The global and internal protein–protein interaction (PPI) networks of the 103 common DEGs consisted of 648 and 14 nodes, respectively. The top 10 hub proteins, namely, ISG15, IRG6, IRF7, IFIT3, MX1, UBE2L6, DDX58, IFIT2, USP18, and IFI44L, drive aspects of DM and AS. MX1 and UBE2L6 were the intersection of internal and global PPI networks. The expression of MX1 and UBE2L6 was 507.22 ± 342.56 and 96.99 ± 49.92 in the HC+STZ group, respectively, which was significantly higher than others and may be linked to the severity of hyperglycaemia-related atherosclerosis. Further PPI network analysis of calcium/micronutrients, including MX1 and UBE2L6, consisted of 58 and 18 nodes, respectively. The most significantly enriched KEGG pathways were glutathione metabolism, pyrimidine metabolism, purine metabolism, and metabolic pathways. Conclusions The global and internal PPI network of the 103 common DEGs consisted of 648 and 14 nodes, respectively. The intersection of the nodes of internal and global PPI networks was MX1 and UBE2L6, suggesting their key role in the comorbidity mechanism of DM and AS. This inference was partly verified by the overexpression of MX1 and UBE2L6 in the HC+STZ group but not others. Further calcium- and micronutrient-related enriched KEGG pathway analysis supported that MX1 and UBE2L6 may affect the inflammatory response through micronutrient metabolic pathways, conceptually named metaflammation. Collectively, MX1 and UBE2L6 may be potential common biomarkers for DM and AS that may reveal metaflammatory aspects of the pathological process, although proper validation is still needed to determine their contribution to the detailed mechanism. |
| first_indexed | 2024-03-07T22:44:16Z |
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| spelling | doaj.art-1be691d668ba433f9ae68abf0788ba0e2024-02-23T15:05:26ZengPeerJ Inc.PeerJ2167-83592024-02-0112e1697510.7717/peerj.16975MX1 and UBE2L6 are potential metaflammation gene targets in both diabetes and atherosclerosisGuisheng Wang0Rongrong Hua1Xiaoxia Chen2Xucheng He3Yao Dingming4Hua Chen5Buhuan Zhang6Yuru Dong7Muqing Liu8Jiaxiong Liu9Ting Liu10Jingwei Zhao11Yu Qiong Zhao12Li Qiao13Department of Radiology, Third Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Radiology, Third Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Radiology, Third Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Radiology, Third Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Radiology, Third Medical Center of Chinese PLA General Hospital, Beijing, ChinaLaboratory Animal Center, Chinese People’s Liberation Army General Hospital, Beijing, ChinaDepartment of Radiology, Third Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Radiology, Third Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Radiology, Third Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Radiology, Third Medical Center of Chinese PLA General Hospital, Beijing, ChinaDepartment of Radiology, Beijing YouAn Hospital, Capital Medical University, Beijing, ChinaDepartment of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaLaboratory Animal Center, Chinese People’s Liberation Army General Hospital, Beijing, ChinaDepartment of International Business, Business College of Beijing Union University, Beijing, ChinaBackground The coexistence of diabetes mellitus (DM) and atherosclerosis (AS) is widespread, although the explicit metabolism and metabolism-associated molecular patterns (MAMPs) responsible for the correlation are still unclear. Methods Twenty-four genetically wild-type male Ba-Ma mini pigs were randomly divided into five groups distinguished by different combinations of 90 mg/kg streptozotocin (STZ) intravenous injection and high-cholesterol/lipid (HC) or high-lipid (HL) diet feeding for 9 months in total. Pigs in the STZ+HC and STZ+HL groups were injected with STZ first and then fed the HC or HL diet for 9 months. In contrast, pigs in the HC+STZ and HL+STZ groups were fed the HC or HL diet for 9 months and injected with STZ at 3 months. The controls were only fed a regular diet for 9 months. The blood glucose and abdominal aortic plaque observed through oil red O staining were used as evaluation indicators for successful modelling of DM and AS. A microarray gene expression analysis of all subjects was performed. Results Atherosclerotic lesions were observed only in the HC+STZ and STZ+HC groups. A total of 103 differentially expressed genes (DEGs) were identified as common between them. The most significantly enriched pathways of 103 common DEGs were influenza A, hepatitis C, and measles. The global and internal protein–protein interaction (PPI) networks of the 103 common DEGs consisted of 648 and 14 nodes, respectively. The top 10 hub proteins, namely, ISG15, IRG6, IRF7, IFIT3, MX1, UBE2L6, DDX58, IFIT2, USP18, and IFI44L, drive aspects of DM and AS. MX1 and UBE2L6 were the intersection of internal and global PPI networks. The expression of MX1 and UBE2L6 was 507.22 ± 342.56 and 96.99 ± 49.92 in the HC+STZ group, respectively, which was significantly higher than others and may be linked to the severity of hyperglycaemia-related atherosclerosis. Further PPI network analysis of calcium/micronutrients, including MX1 and UBE2L6, consisted of 58 and 18 nodes, respectively. The most significantly enriched KEGG pathways were glutathione metabolism, pyrimidine metabolism, purine metabolism, and metabolic pathways. Conclusions The global and internal PPI network of the 103 common DEGs consisted of 648 and 14 nodes, respectively. The intersection of the nodes of internal and global PPI networks was MX1 and UBE2L6, suggesting their key role in the comorbidity mechanism of DM and AS. This inference was partly verified by the overexpression of MX1 and UBE2L6 in the HC+STZ group but not others. Further calcium- and micronutrient-related enriched KEGG pathway analysis supported that MX1 and UBE2L6 may affect the inflammatory response through micronutrient metabolic pathways, conceptually named metaflammation. Collectively, MX1 and UBE2L6 may be potential common biomarkers for DM and AS that may reveal metaflammatory aspects of the pathological process, although proper validation is still needed to determine their contribution to the detailed mechanism.https://peerj.com/articles/16975.pdfDiabetesAtherosclerosisBiomarker signaturesDifferentially expressed genesProtein–protein interaction |
| spellingShingle | Guisheng Wang Rongrong Hua Xiaoxia Chen Xucheng He Yao Dingming Hua Chen Buhuan Zhang Yuru Dong Muqing Liu Jiaxiong Liu Ting Liu Jingwei Zhao Yu Qiong Zhao Li Qiao MX1 and UBE2L6 are potential metaflammation gene targets in both diabetes and atherosclerosis PeerJ Diabetes Atherosclerosis Biomarker signatures Differentially expressed genes Protein–protein interaction |
| title | MX1 and UBE2L6 are potential metaflammation gene targets in both diabetes and atherosclerosis |
| title_full | MX1 and UBE2L6 are potential metaflammation gene targets in both diabetes and atherosclerosis |
| title_fullStr | MX1 and UBE2L6 are potential metaflammation gene targets in both diabetes and atherosclerosis |
| title_full_unstemmed | MX1 and UBE2L6 are potential metaflammation gene targets in both diabetes and atherosclerosis |
| title_short | MX1 and UBE2L6 are potential metaflammation gene targets in both diabetes and atherosclerosis |
| title_sort | mx1 and ube2l6 are potential metaflammation gene targets in both diabetes and atherosclerosis |
| topic | Diabetes Atherosclerosis Biomarker signatures Differentially expressed genes Protein–protein interaction |
| url | https://peerj.com/articles/16975.pdf |
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