Integration of Metabolomics and Proteomics in Exploring the Endothelial Dysfunction Mechanism Induced by Serum Exosomes From Diabetic Retinopathy and Diabetic Nephropathy Patients
BackgroundThe prevalence of diabetic microvascular diseases has increased significantly worldwide, the most common of which are diabetic nephropathy (DN) and diabetic retinopathy (DR). Microvascular endothelial cells are thought to be major targets of hyperglycemic damage, while the underlying mecha...
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.830466/full |
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| author | Jing Yang Jing Yang Jing Yang Jing Yang Dongwei Liu Dongwei Liu Dongwei Liu Dongwei Liu Zhangsuo Liu Zhangsuo Liu Zhangsuo Liu Zhangsuo Liu |
| author_facet | Jing Yang Jing Yang Jing Yang Jing Yang Dongwei Liu Dongwei Liu Dongwei Liu Dongwei Liu Zhangsuo Liu Zhangsuo Liu Zhangsuo Liu Zhangsuo Liu |
| author_sort | Jing Yang |
| collection | DOAJ |
| description | BackgroundThe prevalence of diabetic microvascular diseases has increased significantly worldwide, the most common of which are diabetic nephropathy (DN) and diabetic retinopathy (DR). Microvascular endothelial cells are thought to be major targets of hyperglycemic damage, while the underlying mechanism of diffuse endothelial dysfunction in multiple organs needs to be further investigated.AimThe aim of this study is to explore the endothelial dysfunction mechanisms of serum exosomes (SExos) extracted from DR and DN (DRDN) patients.MethodsIn this study, human glomerular endothelial cells (HGECs) were used as the cell model. Metabolomics ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and proteomics tandem mass tag (TMT)-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) together with bioinformatics, the correlation analysis, and the joint pathway analysis were employed to discover the underlying mechanisms of endothelial dysfunction caused by patient’s SExos.ResultsIt can be assumed that serum exosomes extracted by DRDN patients might cause endothelial dysfunction mainly by upregulating alpha subunit of the coagulation factor fibrinogen (FIBA) and downregulating 1-methylhistidine (1-MH). Bioinformatics analysis pointed to an important role in reducing excess cysteine and methionine metabolism.ConclusionFIBA overexpression and 1-MH loss may be linked to the pathogenicity of diabetic endothelial dysfunction in DR/DN, implying that a cohort study is needed to further investigate the role of FIBA and 1-MH in the development of DN and DR, as well as the related pathways between the two proteins. |
| first_indexed | 2024-12-13T08:58:14Z |
| format | Article |
| id | doaj.art-df2940176b9f485ab0118db363db5517 |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-12-13T08:58:14Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-df2940176b9f485ab0118db363db55172022-12-21T23:53:14ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-03-011310.3389/fendo.2022.830466830466Integration of Metabolomics and Proteomics in Exploring the Endothelial Dysfunction Mechanism Induced by Serum Exosomes From Diabetic Retinopathy and Diabetic Nephropathy PatientsJing Yang0Jing Yang1Jing Yang2Jing Yang3Dongwei Liu4Dongwei Liu5Dongwei Liu6Dongwei Liu7Zhangsuo Liu8Zhangsuo Liu9Zhangsuo Liu10Zhangsuo Liu11Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaResearch Institute of Nephrology, Zhengzhou University, Zhengzhou, ChinaHenan Province Research Center for Kidney Disease, Zhengzhou, ChinaKey Laboratory of Precision Diagnosis and Treatment of Chronic Kidney Disease in Henan Province, Zhengzhou, ChinaResearch Institute of Nephrology, Zhengzhou University, Zhengzhou, ChinaHenan Province Research Center for Kidney Disease, Zhengzhou, ChinaKey Laboratory of Precision Diagnosis and Treatment of Chronic Kidney Disease in Henan Province, Zhengzhou, ChinaDepartment of Integrated Traditional and Western Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaResearch Institute of Nephrology, Zhengzhou University, Zhengzhou, ChinaHenan Province Research Center for Kidney Disease, Zhengzhou, ChinaKey Laboratory of Precision Diagnosis and Treatment of Chronic Kidney Disease in Henan Province, Zhengzhou, ChinaDepartment of Integrated Traditional and Western Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaBackgroundThe prevalence of diabetic microvascular diseases has increased significantly worldwide, the most common of which are diabetic nephropathy (DN) and diabetic retinopathy (DR). Microvascular endothelial cells are thought to be major targets of hyperglycemic damage, while the underlying mechanism of diffuse endothelial dysfunction in multiple organs needs to be further investigated.AimThe aim of this study is to explore the endothelial dysfunction mechanisms of serum exosomes (SExos) extracted from DR and DN (DRDN) patients.MethodsIn this study, human glomerular endothelial cells (HGECs) were used as the cell model. Metabolomics ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and proteomics tandem mass tag (TMT)-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) together with bioinformatics, the correlation analysis, and the joint pathway analysis were employed to discover the underlying mechanisms of endothelial dysfunction caused by patient’s SExos.ResultsIt can be assumed that serum exosomes extracted by DRDN patients might cause endothelial dysfunction mainly by upregulating alpha subunit of the coagulation factor fibrinogen (FIBA) and downregulating 1-methylhistidine (1-MH). Bioinformatics analysis pointed to an important role in reducing excess cysteine and methionine metabolism.ConclusionFIBA overexpression and 1-MH loss may be linked to the pathogenicity of diabetic endothelial dysfunction in DR/DN, implying that a cohort study is needed to further investigate the role of FIBA and 1-MH in the development of DN and DR, as well as the related pathways between the two proteins.https://www.frontiersin.org/articles/10.3389/fendo.2022.830466/fullmetabolomicsproteomicsexosomesdiabetic nephropathydiabetic retinopathyendothelial dysfunction |
| spellingShingle | Jing Yang Jing Yang Jing Yang Jing Yang Dongwei Liu Dongwei Liu Dongwei Liu Dongwei Liu Zhangsuo Liu Zhangsuo Liu Zhangsuo Liu Zhangsuo Liu Integration of Metabolomics and Proteomics in Exploring the Endothelial Dysfunction Mechanism Induced by Serum Exosomes From Diabetic Retinopathy and Diabetic Nephropathy Patients Frontiers in Endocrinology metabolomics proteomics exosomes diabetic nephropathy diabetic retinopathy endothelial dysfunction |
| title | Integration of Metabolomics and Proteomics in Exploring the Endothelial Dysfunction Mechanism Induced by Serum Exosomes From Diabetic Retinopathy and Diabetic Nephropathy Patients |
| title_full | Integration of Metabolomics and Proteomics in Exploring the Endothelial Dysfunction Mechanism Induced by Serum Exosomes From Diabetic Retinopathy and Diabetic Nephropathy Patients |
| title_fullStr | Integration of Metabolomics and Proteomics in Exploring the Endothelial Dysfunction Mechanism Induced by Serum Exosomes From Diabetic Retinopathy and Diabetic Nephropathy Patients |
| title_full_unstemmed | Integration of Metabolomics and Proteomics in Exploring the Endothelial Dysfunction Mechanism Induced by Serum Exosomes From Diabetic Retinopathy and Diabetic Nephropathy Patients |
| title_short | Integration of Metabolomics and Proteomics in Exploring the Endothelial Dysfunction Mechanism Induced by Serum Exosomes From Diabetic Retinopathy and Diabetic Nephropathy Patients |
| title_sort | integration of metabolomics and proteomics in exploring the endothelial dysfunction mechanism induced by serum exosomes from diabetic retinopathy and diabetic nephropathy patients |
| topic | metabolomics proteomics exosomes diabetic nephropathy diabetic retinopathy endothelial dysfunction |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.830466/full |
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