Identification of Dysregulated Complement Activation Pathways Driven by N-Glycosylation Alterations in T2D Patients
Diabetes has become a major public health concern worldwide, most of which are type 2 diabetes (T2D). The diagnosis of T2D is commonly based on plasma glucose levels, and there are no reliable clinical biomarkers available for early detection. Recent advances in proteome technologies offer new oppor...
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2021.677621/full |
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| author | Yang Zhao Man Wang Man Wang Bo Meng Ying Gao Zhichao Xue Minjun He You Jiang Xinhua Dai Dan Yan Dan Yan Dan Yan Xiang Fang |
| author_facet | Yang Zhao Man Wang Man Wang Bo Meng Ying Gao Zhichao Xue Minjun He You Jiang Xinhua Dai Dan Yan Dan Yan Dan Yan Xiang Fang |
| author_sort | Yang Zhao |
| collection | DOAJ |
| description | Diabetes has become a major public health concern worldwide, most of which are type 2 diabetes (T2D). The diagnosis of T2D is commonly based on plasma glucose levels, and there are no reliable clinical biomarkers available for early detection. Recent advances in proteome technologies offer new opportunity for the understanding of T2D; however, the underlying proteomic characteristics of T2D have not been thoroughly investigated yet. Here, using proteomic and glycoproteomic profiling, we provided a comprehensive landscape of molecular alterations in the fasting plasma of the 24 Chinese participants, including eight T2D patients, eight prediabetic (PDB) subjects, and eight healthy control (HC) individuals. Our analyses identified a diverse set of potential biomarkers that might enhance the efficiency and accuracy based on current existing biological indicators of (pre)diabetes. Through integrative omics analysis, we showed the capability of glycoproteomics as a complement to proteomics or metabolomics, to provide additional insights into the pathogenesis of (pre)diabetes. We have newly identified systemic site-specific N-glycosylation alterations underlying T2D patients in the complement activation pathways, including decreased levels of N-glycopeptides from C1s, MASP1, and CFP proteins, and increased levels of N-glycopeptides from C2, C4, C4BPA, C4BPB, and CFH. These alterations were not observed at proteomic levels, suggesting new opportunities for the diagnosis and treatment of this disease. Our results demonstrate a great potential role of glycoproteomics in understanding (pre)diabetes and present a new direction for diabetes research which deserves more attention. |
| first_indexed | 2024-12-16T11:17:18Z |
| format | Article |
| id | doaj.art-b9ac40b251c4440ba10db62d0c385434 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-16T11:17:18Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-b9ac40b251c4440ba10db62d0c3854342022-12-21T22:33:34ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462021-06-01910.3389/fchem.2021.677621677621Identification of Dysregulated Complement Activation Pathways Driven by N-Glycosylation Alterations in T2D PatientsYang Zhao0Man Wang1Man Wang2Bo Meng3Ying Gao4Zhichao Xue5Minjun He6You Jiang7Xinhua Dai8Dan Yan9Dan Yan10Dan Yan11Xiang Fang12Center for Advanced Measurement Science, National Institute of Metrology, Beijing, ChinaCenter for Advanced Measurement Science, National Institute of Metrology, Beijing, ChinaCollege of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaCenter for Advanced Measurement Science, National Institute of Metrology, Beijing, ChinaCenter for Advanced Measurement Science, National Institute of Metrology, Beijing, ChinaCenter for Advanced Measurement Science, National Institute of Metrology, Beijing, ChinaCenter for Advanced Measurement Science, National Institute of Metrology, Beijing, ChinaCenter for Advanced Measurement Science, National Institute of Metrology, Beijing, ChinaCenter for Advanced Measurement Science, National Institute of Metrology, Beijing, ChinaCollege of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, ChinaBeijing Key Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaCenter for Advanced Measurement Science, National Institute of Metrology, Beijing, ChinaDiabetes has become a major public health concern worldwide, most of which are type 2 diabetes (T2D). The diagnosis of T2D is commonly based on plasma glucose levels, and there are no reliable clinical biomarkers available for early detection. Recent advances in proteome technologies offer new opportunity for the understanding of T2D; however, the underlying proteomic characteristics of T2D have not been thoroughly investigated yet. Here, using proteomic and glycoproteomic profiling, we provided a comprehensive landscape of molecular alterations in the fasting plasma of the 24 Chinese participants, including eight T2D patients, eight prediabetic (PDB) subjects, and eight healthy control (HC) individuals. Our analyses identified a diverse set of potential biomarkers that might enhance the efficiency and accuracy based on current existing biological indicators of (pre)diabetes. Through integrative omics analysis, we showed the capability of glycoproteomics as a complement to proteomics or metabolomics, to provide additional insights into the pathogenesis of (pre)diabetes. We have newly identified systemic site-specific N-glycosylation alterations underlying T2D patients in the complement activation pathways, including decreased levels of N-glycopeptides from C1s, MASP1, and CFP proteins, and increased levels of N-glycopeptides from C2, C4, C4BPA, C4BPB, and CFH. These alterations were not observed at proteomic levels, suggesting new opportunities for the diagnosis and treatment of this disease. Our results demonstrate a great potential role of glycoproteomics in understanding (pre)diabetes and present a new direction for diabetes research which deserves more attention.https://www.frontiersin.org/articles/10.3389/fchem.2021.677621/fullproteomicsglycoproteomicsN-glycopeptidesdiabetescomplement |
| spellingShingle | Yang Zhao Man Wang Man Wang Bo Meng Ying Gao Zhichao Xue Minjun He You Jiang Xinhua Dai Dan Yan Dan Yan Dan Yan Xiang Fang Identification of Dysregulated Complement Activation Pathways Driven by N-Glycosylation Alterations in T2D Patients Frontiers in Chemistry proteomics glycoproteomics N-glycopeptides diabetes complement |
| title | Identification of Dysregulated Complement Activation Pathways Driven by N-Glycosylation Alterations in T2D Patients |
| title_full | Identification of Dysregulated Complement Activation Pathways Driven by N-Glycosylation Alterations in T2D Patients |
| title_fullStr | Identification of Dysregulated Complement Activation Pathways Driven by N-Glycosylation Alterations in T2D Patients |
| title_full_unstemmed | Identification of Dysregulated Complement Activation Pathways Driven by N-Glycosylation Alterations in T2D Patients |
| title_short | Identification of Dysregulated Complement Activation Pathways Driven by N-Glycosylation Alterations in T2D Patients |
| title_sort | identification of dysregulated complement activation pathways driven by n glycosylation alterations in t2d patients |
| topic | proteomics glycoproteomics N-glycopeptides diabetes complement |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2021.677621/full |
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