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Analysis of the differential urinary protein profile in IgA nephropathy patients of Uygur ethnicity

BACKGROUND: IgA nephropathy (IgAN) is one of the most common forms of idiopathic glomerular diseases and might lead to end-stage kidney disease. Accurate and non-invasive biomarkers for early diagnosis are required for early intervention and consequent therapy for IgAN patients. Because variance in...

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Autores principales: Guo, Zhengguang, Wang, Zhao, Lu, Chen, Yang, Shufen, Sun, Haidan, Reziw, Guo, Yu, Sun, Wei, Yue, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295011/
https://www.ncbi.nlm.nih.gov/pubmed/30547763
http://dx.doi.org/10.1186/s12882-018-1139-3
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author Guo, Zhengguang
Wang, Zhao
Lu, Chen
Yang, Shufen
Sun, Haidan
Reziw
Guo, Yu
Sun, Wei
Yue, Hua
author_facet Guo, Zhengguang
Wang, Zhao
Lu, Chen
Yang, Shufen
Sun, Haidan
Reziw
Guo, Yu
Sun, Wei
Yue, Hua
author_sort Guo, Zhengguang
collection PubMed
description BACKGROUND: IgA nephropathy (IgAN) is one of the most common forms of idiopathic glomerular diseases and might lead to end-stage kidney disease. Accurate and non-invasive biomarkers for early diagnosis are required for early intervention and consequent therapy for IgAN patients. Because variance in the disease incidence and predisposing genes of IgAN has been detected among different ethnicities, the ethnicity factor should be considered in IgAN biomarker discovery. The differences in the protein profiles and pathological mechanisms of IgAN in patients of Uygur ethnicity need to be clearly illustrated. METHODS: In this study, we used urinary proteomics to discover candidate biomarkers of IgAN in patients of Uygur ethnicity. The urinary proteins from Uygur normal control and Uygur IgAN patients were extracted and analyzed using 2D-LC-MS/MS and isobaric tags for relative and absolute quantitation (iTRAQ) analysis. RESULTS: A total of 277 proteins were found to be differentially represented in Uygur IgAN compared with the respective normal controls. The bioinformatics analysis revealed that the immune response, cell survival, and complement system were activated in Uygur IgAN. Many differentially expressed proteins were found to be related to nephropathy and kidney injuries. Four candidate biomarkers were validated by Western blot, and these results were consistent with the iTRAQ results. ICAM1, TIMP1, SERPINC1 and ADIPOQ were upregulated in Uygur IgAN. Bioinformatic analysis revealed that the increase of ICAM1 and TIMP1 might be caused by IgAN, but the increase of SERPINC1 and ADIPOQ might be caused by proteinuria. SERPINC1 and ICAM1 were identified as the candidate biomarkers with excellent area-under-the-curve (AUC) values (0.84) for distinguishing Uygur IgAN from normal controls. CONCLUSIONS: Using urinary proteomic analysis, we identified several candidate biomarkers for IgAN in patients of Uygur ethnicity. These results will prove helpful for exploring the pathological mechanism of IgAN in patients of Uygur ethnicity and for developing better treatments for these patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12882-018-1139-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-62950112018-12-18 Analysis of the differential urinary protein profile in IgA nephropathy patients of Uygur ethnicity Guo, Zhengguang Wang, Zhao Lu, Chen Yang, Shufen Sun, Haidan Reziw Guo, Yu Sun, Wei Yue, Hua BMC Nephrol Research Article BACKGROUND: IgA nephropathy (IgAN) is one of the most common forms of idiopathic glomerular diseases and might lead to end-stage kidney disease. Accurate and non-invasive biomarkers for early diagnosis are required for early intervention and consequent therapy for IgAN patients. Because variance in the disease incidence and predisposing genes of IgAN has been detected among different ethnicities, the ethnicity factor should be considered in IgAN biomarker discovery. The differences in the protein profiles and pathological mechanisms of IgAN in patients of Uygur ethnicity need to be clearly illustrated. METHODS: In this study, we used urinary proteomics to discover candidate biomarkers of IgAN in patients of Uygur ethnicity. The urinary proteins from Uygur normal control and Uygur IgAN patients were extracted and analyzed using 2D-LC-MS/MS and isobaric tags for relative and absolute quantitation (iTRAQ) analysis. RESULTS: A total of 277 proteins were found to be differentially represented in Uygur IgAN compared with the respective normal controls. The bioinformatics analysis revealed that the immune response, cell survival, and complement system were activated in Uygur IgAN. Many differentially expressed proteins were found to be related to nephropathy and kidney injuries. Four candidate biomarkers were validated by Western blot, and these results were consistent with the iTRAQ results. ICAM1, TIMP1, SERPINC1 and ADIPOQ were upregulated in Uygur IgAN. Bioinformatic analysis revealed that the increase of ICAM1 and TIMP1 might be caused by IgAN, but the increase of SERPINC1 and ADIPOQ might be caused by proteinuria. SERPINC1 and ICAM1 were identified as the candidate biomarkers with excellent area-under-the-curve (AUC) values (0.84) for distinguishing Uygur IgAN from normal controls. CONCLUSIONS: Using urinary proteomic analysis, we identified several candidate biomarkers for IgAN in patients of Uygur ethnicity. These results will prove helpful for exploring the pathological mechanism of IgAN in patients of Uygur ethnicity and for developing better treatments for these patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12882-018-1139-3) contains supplementary material, which is available to authorized users. BioMed Central 2018-12-14 /pmc/articles/PMC6295011/ /pubmed/30547763 http://dx.doi.org/10.1186/s12882-018-1139-3 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Guo, Zhengguang
Wang, Zhao
Lu, Chen
Yang, Shufen
Sun, Haidan
Reziw
Guo, Yu
Sun, Wei
Yue, Hua
Analysis of the differential urinary protein profile in IgA nephropathy patients of Uygur ethnicity
title Analysis of the differential urinary protein profile in IgA nephropathy patients of Uygur ethnicity
title_full Analysis of the differential urinary protein profile in IgA nephropathy patients of Uygur ethnicity
title_fullStr Analysis of the differential urinary protein profile in IgA nephropathy patients of Uygur ethnicity
title_full_unstemmed Analysis of the differential urinary protein profile in IgA nephropathy patients of Uygur ethnicity
title_short Analysis of the differential urinary protein profile in IgA nephropathy patients of Uygur ethnicity
title_sort analysis of the differential urinary protein profile in iga nephropathy patients of uygur ethnicity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295011/
https://www.ncbi.nlm.nih.gov/pubmed/30547763
http://dx.doi.org/10.1186/s12882-018-1139-3
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