文献类型：期刊文献

英文题名：MX1 and UBE2L6 are potential metaflammation gene targets in both diabetes and atherosclerosis

作者：Wang, Guisheng[1];Hua, Rongrong[1];Chen, Xiaoxia[1];He, Xucheng[1];Yao, Dingming[1];Chen, Hua[2];Zhang, Buhuan[1];Dong, Yuru[1];Liu, Muqing[1];Liu, Jiaxiong[1];Liu, Ting[3];Zhao, Jingwei[4];Zhao, Yu Qiong[2];Qiao, Li[5]

第一作者：Wang, Guisheng

通讯作者：Zhao, YQ[1];Qiao, L[2]

机构：[1]Chinese Peoples Liberat Army Gen Hosp, Dept Radiol, Med Ctr 3, Beijing, Peoples R China;[2]Chinese Peoples Liberat Army Gen Hosp, Lab Anim Ctr, Beijing, Peoples R China;[3]Capital Med Univ, Beijing YouAn Hosp, Dept Radiol, Beijing, Peoples R China;[4]Canc Hosp, Chinese Acad Med Sci & Peking Union Med Coll, Dept Radiol,Natl Clin Res Ctr Canc, Beijing, Peoples R China;[5]Beijing Union Univ, Business Coll, Dept Int Business, Beijing, Peoples R China

第一机构：Chinese Peoples Liberat Army Gen Hosp, Dept Radiol, Med Ctr 3, Beijing, Peoples R China

通讯机构：[1]corresponding author), Chinese Peoples Liberat Army Gen Hosp, Lab Anim Ctr, Beijing, Peoples R China;[2]corresponding author), Beijing Union Univ, Business Coll, Dept Int Business, Beijing, Peoples R China.|[1141721]北京联合大学商务学院;[11417]北京联合大学;

年份：2024

卷号：12

外文期刊名：PEERJ

收录：;Scopus(收录号：2-s2.0-85185798842);WOS:【SCI-EXPANDED(收录号:WOS:001171802200004)】；

基金：This work was supported by the National Key R8rD Program of China (No. 2022YFB4702602) , the Beijing Natural Science Foundation (7222319) , the Beijing Municipal Science 8r Technology Commission (Z21100002921047) , and the National Natural Science Foundation of China (NSFC 82001808) . The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

语种：英文

外文关键词：Diabetes; Atherosclerosis; Biomarker signatures; Differentially expressed genes; Protein-protein interaction

摘要：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.