Exploring the shared molecular mechanism of microvascular and macrovascular complications in diabetes: Seeking the hub of circulatory system injury
BackgroundMicrovascular complications, such as diabetic retinopathy (DR) and diabetic nephropathy (DN), and macrovascular complications, referring to atherosclerosis (AS), are the main complications of diabetes. Blindness or fatal microvascular diseases are considered to be identified earlier than f...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1032015/full |
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| author | Cao Yuchen Cao Yuchen Cao Yuchen Zhao Hejia Meng Fanke Meng Fanke Deng Qixin Cai Liyang Cai Liyang Guo Xi Guo Xi Guo Xi Chen Yanxia Chen Yanxia Yang Xiongyi Yang Xiongyi Xie Zhuohang Xie Zhuohang Yi Guoguo Fu Min Fu Min |
| author_facet | Cao Yuchen Cao Yuchen Cao Yuchen Zhao Hejia Meng Fanke Meng Fanke Deng Qixin Cai Liyang Cai Liyang Guo Xi Guo Xi Guo Xi Chen Yanxia Chen Yanxia Yang Xiongyi Yang Xiongyi Xie Zhuohang Xie Zhuohang Yi Guoguo Fu Min Fu Min |
| author_sort | Cao Yuchen |
| collection | DOAJ |
| description | BackgroundMicrovascular complications, such as diabetic retinopathy (DR) and diabetic nephropathy (DN), and macrovascular complications, referring to atherosclerosis (AS), are the main complications of diabetes. Blindness or fatal microvascular diseases are considered to be identified earlier than fatal macrovascular complications. Exploring the intrinsic relationship between microvascular and macrovascular complications and the hub of pathogenesis is of vital importance for prolonging the life span of patients with diabetes and improving the quality of life.Materials and methodsThe expression profiles of GSE28829, GSE30529, GSE146615 and GSE134998 were downloaded from the Gene Expression Omnibus database, which contained 29 atherosclerotic plaque samples, including 16 AS samples and 13 normal controls; 22 renal glomeruli and tubules samples from diabetes nephropathy including 12 DN samples and 10 normal controls; 73 lymphoblastoid cell line samples, including 52 DR samples and 21 normal controls. The microarray datasets were consolidated and DEGs were acquired and further analyzed by bioinformatics techniques including GSEA analysis, GO-KEGG functional clustering by R (version 4.0.5), PPI analysis by Cytoscape (version 3.8.2) and String database, miRNA analysis by Diana database, and hub genes analysis by Metascape database. The drug sensitivity of characteristic DEGs was analyzed.ResultA total of 3709, 4185 and 8086 DEGs were recognized in AS, DN, DR, respectively, with 1820, 1666, 888 upregulated and 1889, 2519, 7198 downregulated. GO and KEGG pathway analyses of DEGs and GSEA analysis of common differential genes demonstrated that these significant sites focused primarily on inflammation-oxidative stress and immune regulation pathways. PPI networks show the connection and regulation on top-250 significant sites of AS, DN, DR. MiRNA analysis explored the non-coding RNA upstream regulation network and significant pathway in AS, DN, DR. The joint analysis of multiple diseases shows the common influenced pathways of AS, DN, DR and explored the interaction between top-1000 DEGs at the same time.ConclusionIn the microvascular and macrovascular complications of diabetes, immune-mediated inflammatory response, chronic inflammation caused by endothelial cell activation and oxidative stress are the three links linking atherosclerosis, diabetes retinopathy and diabetes nephropathy together. Our study has clarified the intrinsic relationship and common tissue damage mechanism of microcirculation and circulatory system complications in diabetes, and explored the mechanism center of these two vascular complications. It has far-reaching clinical and social value for reducing the incidence of fatal events and early controlling the progress of disabling and fatal circulatory complications in diabetes. |
| first_indexed | 2024-04-10T20:55:13Z |
| format | Article |
| id | doaj.art-13d5b67602404fa2b2c72356a52b7563 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-10T20:55:13Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-13d5b67602404fa2b2c72356a52b75632023-01-23T05:40:16ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-01-011410.3389/fendo.2023.10320151032015Exploring the shared molecular mechanism of microvascular and macrovascular complications in diabetes: Seeking the hub of circulatory system injuryCao Yuchen0Cao Yuchen1Cao Yuchen2Zhao Hejia3Meng Fanke4Meng Fanke5Deng Qixin6Cai Liyang7Cai Liyang8Guo Xi9Guo Xi10Guo Xi11Chen Yanxia12Chen Yanxia13Yang Xiongyi14Yang Xiongyi15Xie Zhuohang16Xie Zhuohang17Yi Guoguo18Fu Min19Fu Min20Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaThe Second Clinical School, Southern Medical University, Guangzhou, ChinaPlastic Surgery Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaSchool of Public Health, Southern Medical University, Guangzhou, ChinaThe Second Clinical School, Southern Medical University, Guangzhou, ChinaDepartment of Emergency, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaThe Second Clinical School, Southern Medical University, Guangzhou, ChinaDepartment of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaSchool of Rehabilitation Sciences, Southern Medical University, Guangzhou, Guangdong, ChinaSchool of Psychological and Cognitive Sciences and Beijing Key Laboratory of Behavior and Mental Health, Peking University, Beijing, ChinaDepartment of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaThe Second Clinical School, Southern Medical University, Guangzhou, ChinaDepartment of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaThe Second Clinical School, Southern Medical University, Guangzhou, ChinaDepartment of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaThe Second Clinical School, Southern Medical University, Guangzhou, ChinaDepartment of Ophthalmology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaThe Second Clinical School, Southern Medical University, Guangzhou, ChinaBackgroundMicrovascular complications, such as diabetic retinopathy (DR) and diabetic nephropathy (DN), and macrovascular complications, referring to atherosclerosis (AS), are the main complications of diabetes. Blindness or fatal microvascular diseases are considered to be identified earlier than fatal macrovascular complications. Exploring the intrinsic relationship between microvascular and macrovascular complications and the hub of pathogenesis is of vital importance for prolonging the life span of patients with diabetes and improving the quality of life.Materials and methodsThe expression profiles of GSE28829, GSE30529, GSE146615 and GSE134998 were downloaded from the Gene Expression Omnibus database, which contained 29 atherosclerotic plaque samples, including 16 AS samples and 13 normal controls; 22 renal glomeruli and tubules samples from diabetes nephropathy including 12 DN samples and 10 normal controls; 73 lymphoblastoid cell line samples, including 52 DR samples and 21 normal controls. The microarray datasets were consolidated and DEGs were acquired and further analyzed by bioinformatics techniques including GSEA analysis, GO-KEGG functional clustering by R (version 4.0.5), PPI analysis by Cytoscape (version 3.8.2) and String database, miRNA analysis by Diana database, and hub genes analysis by Metascape database. The drug sensitivity of characteristic DEGs was analyzed.ResultA total of 3709, 4185 and 8086 DEGs were recognized in AS, DN, DR, respectively, with 1820, 1666, 888 upregulated and 1889, 2519, 7198 downregulated. GO and KEGG pathway analyses of DEGs and GSEA analysis of common differential genes demonstrated that these significant sites focused primarily on inflammation-oxidative stress and immune regulation pathways. PPI networks show the connection and regulation on top-250 significant sites of AS, DN, DR. MiRNA analysis explored the non-coding RNA upstream regulation network and significant pathway in AS, DN, DR. The joint analysis of multiple diseases shows the common influenced pathways of AS, DN, DR and explored the interaction between top-1000 DEGs at the same time.ConclusionIn the microvascular and macrovascular complications of diabetes, immune-mediated inflammatory response, chronic inflammation caused by endothelial cell activation and oxidative stress are the three links linking atherosclerosis, diabetes retinopathy and diabetes nephropathy together. Our study has clarified the intrinsic relationship and common tissue damage mechanism of microcirculation and circulatory system complications in diabetes, and explored the mechanism center of these two vascular complications. It has far-reaching clinical and social value for reducing the incidence of fatal events and early controlling the progress of disabling and fatal circulatory complications in diabetes.https://www.frontiersin.org/articles/10.3389/fendo.2023.1032015/fullatherosclerosisdiabetic retinopathydiabetic nephropathycomplications of circulatory systeminflammation-oxidative stressimmune regulation |
| spellingShingle | Cao Yuchen Cao Yuchen Cao Yuchen Zhao Hejia Meng Fanke Meng Fanke Deng Qixin Cai Liyang Cai Liyang Guo Xi Guo Xi Guo Xi Chen Yanxia Chen Yanxia Yang Xiongyi Yang Xiongyi Xie Zhuohang Xie Zhuohang Yi Guoguo Fu Min Fu Min Exploring the shared molecular mechanism of microvascular and macrovascular complications in diabetes: Seeking the hub of circulatory system injury Frontiers in Endocrinology atherosclerosis diabetic retinopathy diabetic nephropathy complications of circulatory system inflammation-oxidative stress immune regulation |
| title | Exploring the shared molecular mechanism of microvascular and macrovascular complications in diabetes: Seeking the hub of circulatory system injury |
| title_full | Exploring the shared molecular mechanism of microvascular and macrovascular complications in diabetes: Seeking the hub of circulatory system injury |
| title_fullStr | Exploring the shared molecular mechanism of microvascular and macrovascular complications in diabetes: Seeking the hub of circulatory system injury |
| title_full_unstemmed | Exploring the shared molecular mechanism of microvascular and macrovascular complications in diabetes: Seeking the hub of circulatory system injury |
| title_short | Exploring the shared molecular mechanism of microvascular and macrovascular complications in diabetes: Seeking the hub of circulatory system injury |
| title_sort | exploring the shared molecular mechanism of microvascular and macrovascular complications in diabetes seeking the hub of circulatory system injury |
| topic | atherosclerosis diabetic retinopathy diabetic nephropathy complications of circulatory system inflammation-oxidative stress immune regulation |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1032015/full |
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