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Urinary complement proteins in IgA nephropathy progression from a relative quantitative proteomic analysis

AIM: IgA nephropathy (IgAN) is one of the leading causes of end-stage renal disease (ESRD). Urine testing is a non-invasive way to track the biomarkers used for measuring renal injury. This study aimed to analyse urinary complement proteins during IgAN progression using quantitative proteomics. METH...

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Autores principales: Niu, Xia, Zhang, Shuyu, Shao, Chen, Guo, Zhengguang, Wu, Jianqiang, Tao, Jianling, Zheng, Ke, Ye, Wenling, Cai, Guangyan, Sun, Wei, Li, Mingxi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10103701/
https://www.ncbi.nlm.nih.gov/pubmed/37065697
http://dx.doi.org/10.7717/peerj.15125
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author Niu, Xia
Zhang, Shuyu
Shao, Chen
Guo, Zhengguang
Wu, Jianqiang
Tao, Jianling
Zheng, Ke
Ye, Wenling
Cai, Guangyan
Sun, Wei
Li, Mingxi
author_facet Niu, Xia
Zhang, Shuyu
Shao, Chen
Guo, Zhengguang
Wu, Jianqiang
Tao, Jianling
Zheng, Ke
Ye, Wenling
Cai, Guangyan
Sun, Wei
Li, Mingxi
author_sort Niu, Xia
collection PubMed
description AIM: IgA nephropathy (IgAN) is one of the leading causes of end-stage renal disease (ESRD). Urine testing is a non-invasive way to track the biomarkers used for measuring renal injury. This study aimed to analyse urinary complement proteins during IgAN progression using quantitative proteomics. METHODS: In the discovery phase, we analysed 22 IgAN patients who were divided into three groups (IgAN 1-3) according to their estimated glomerular filtration rate (eGFR). Eight patients with primary membranous nephropathy (pMN) were used as controls. Isobaric tags for relative and absolute quantitation (iTRAQ) labelling, coupled with liquid chromatography-tandem mass spectrometry, was used to analyse global urinary protein expression. In the validation phase, western blotting and parallel reaction monitoring (PRM) were used to verify the iTRAQ results in an independent cohort (N = 64). RESULTS: In the discovery phase, 747 proteins were identified in the urine of IgAN and pMN patients. There were different urine protein profiles in IgAN and pMN patients, and the bioinformatics analysis revealed that the complement and coagulation pathways were most activated. We identified a total of 27 urinary complement proteins related to IgAN. The relative abundance of C3, the membrane attack complex (MAC), the complement regulatory proteins of the alternative pathway (AP), and MBL (mannose-binding lectin) and MASP1 (MBL associated serine protease 2) in the lectin pathway (LP) increased during IgAN progression. This was especially true for MAC, which was found to be involved prominently in disease progression. Alpha-N-acetylglucosaminidase (NAGLU) and α-galactosidase A (GLA) were validated by western blot and the results were consistent with the iTRAQ results. Ten proteins were validated in a PRM analysis, and these results were also consistent with the iTRAQ results. Complement factor B (CFB) and complement component C8 alpha chain (C8A) both increased with the progression of IgAN. The combination of CFB and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) also showed potential as a urinary biomarker for monitoring IgAN development. CONCLUSION: There were abundant complement components in the urine of IgAN patients, indicating that the activation of AP and LP is involved in IgAN progression. Urinary complement proteins may be used as biomarkers for evaluating IgAN progression in the future.
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spelling pubmed-101037012023-04-15 Urinary complement proteins in IgA nephropathy progression from a relative quantitative proteomic analysis Niu, Xia Zhang, Shuyu Shao, Chen Guo, Zhengguang Wu, Jianqiang Tao, Jianling Zheng, Ke Ye, Wenling Cai, Guangyan Sun, Wei Li, Mingxi PeerJ Immunology AIM: IgA nephropathy (IgAN) is one of the leading causes of end-stage renal disease (ESRD). Urine testing is a non-invasive way to track the biomarkers used for measuring renal injury. This study aimed to analyse urinary complement proteins during IgAN progression using quantitative proteomics. METHODS: In the discovery phase, we analysed 22 IgAN patients who were divided into three groups (IgAN 1-3) according to their estimated glomerular filtration rate (eGFR). Eight patients with primary membranous nephropathy (pMN) were used as controls. Isobaric tags for relative and absolute quantitation (iTRAQ) labelling, coupled with liquid chromatography-tandem mass spectrometry, was used to analyse global urinary protein expression. In the validation phase, western blotting and parallel reaction monitoring (PRM) were used to verify the iTRAQ results in an independent cohort (N = 64). RESULTS: In the discovery phase, 747 proteins were identified in the urine of IgAN and pMN patients. There were different urine protein profiles in IgAN and pMN patients, and the bioinformatics analysis revealed that the complement and coagulation pathways were most activated. We identified a total of 27 urinary complement proteins related to IgAN. The relative abundance of C3, the membrane attack complex (MAC), the complement regulatory proteins of the alternative pathway (AP), and MBL (mannose-binding lectin) and MASP1 (MBL associated serine protease 2) in the lectin pathway (LP) increased during IgAN progression. This was especially true for MAC, which was found to be involved prominently in disease progression. Alpha-N-acetylglucosaminidase (NAGLU) and α-galactosidase A (GLA) were validated by western blot and the results were consistent with the iTRAQ results. Ten proteins were validated in a PRM analysis, and these results were also consistent with the iTRAQ results. Complement factor B (CFB) and complement component C8 alpha chain (C8A) both increased with the progression of IgAN. The combination of CFB and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) also showed potential as a urinary biomarker for monitoring IgAN development. CONCLUSION: There were abundant complement components in the urine of IgAN patients, indicating that the activation of AP and LP is involved in IgAN progression. Urinary complement proteins may be used as biomarkers for evaluating IgAN progression in the future. PeerJ Inc. 2023-04-11 /pmc/articles/PMC10103701/ /pubmed/37065697 http://dx.doi.org/10.7717/peerj.15125 Text en © 2023 Niu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Immunology
Niu, Xia
Zhang, Shuyu
Shao, Chen
Guo, Zhengguang
Wu, Jianqiang
Tao, Jianling
Zheng, Ke
Ye, Wenling
Cai, Guangyan
Sun, Wei
Li, Mingxi
Urinary complement proteins in IgA nephropathy progression from a relative quantitative proteomic analysis
title Urinary complement proteins in IgA nephropathy progression from a relative quantitative proteomic analysis
title_full Urinary complement proteins in IgA nephropathy progression from a relative quantitative proteomic analysis
title_fullStr Urinary complement proteins in IgA nephropathy progression from a relative quantitative proteomic analysis
title_full_unstemmed Urinary complement proteins in IgA nephropathy progression from a relative quantitative proteomic analysis
title_short Urinary complement proteins in IgA nephropathy progression from a relative quantitative proteomic analysis
title_sort urinary complement proteins in iga nephropathy progression from a relative quantitative proteomic analysis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10103701/
https://www.ncbi.nlm.nih.gov/pubmed/37065697
http://dx.doi.org/10.7717/peerj.15125
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