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. Metho...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
PeerJ Inc.
2023-04-01
|
| Series: | PeerJ |
| Subjects: | |
| Online Access: | https://peerj.com/articles/15125.pdf |
| _version_ | 1797419630025768960 |
|---|---|
| author | Xia Niu Shuyu Zhang Chen Shao Zhengguang Guo Jianqiang Wu Jianling Tao Ke Zheng Wenling Ye Guangyan Cai Wei Sun Mingxi Li |
| author_facet | Xia Niu Shuyu Zhang Chen Shao Zhengguang Guo Jianqiang Wu Jianling Tao Ke Zheng Wenling Ye Guangyan Cai Wei Sun Mingxi Li |
| author_sort | Xia Niu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T06:50:01Z |
| format | Article |
| id | doaj.art-4fba0a3a496144bbaac4f6c594bb0b3d |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T06:50:01Z |
| publishDate | 2023-04-01 |
| publisher | PeerJ Inc. |
| record_format | Article |
| series | PeerJ |
| spelling | doaj.art-4fba0a3a496144bbaac4f6c594bb0b3d2023-12-03T10:28:52ZengPeerJ Inc.PeerJ2167-83592023-04-0111e1512510.7717/peerj.15125Urinary complement proteins in IgA nephropathy progression from a relative quantitative proteomic analysisXia Niu0Shuyu Zhang1Chen Shao2Zhengguang Guo3Jianqiang Wu4Jianling Tao5Ke Zheng6Wenling Ye7Guangyan Cai8Wei Sun9Mingxi Li10Core Facility of Instruments, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, ChinaDepartment of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, ChinaCore Facility of Instruments, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, ChinaCore Facility of Instruments, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, ChinaMedical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, ChinaDepartment of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, ChinaDepartment of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, ChinaDepartment of Nephrology, The First Medical Centre, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, ChinaCore Facility of Instruments, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, ChinaDepartment of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, ChinaAim 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.https://peerj.com/articles/15125.pdfComplement proteinsIgA nephropathyα-N-acetylglucosaminidaseProteomicsUrine |
| spellingShingle | Xia Niu Shuyu Zhang Chen Shao Zhengguang Guo Jianqiang Wu Jianling Tao Ke Zheng Wenling Ye Guangyan Cai Wei Sun Mingxi Li Urinary complement proteins in IgA nephropathy progression from a relative quantitative proteomic analysis PeerJ Complement proteins IgA nephropathy α-N-acetylglucosaminidase Proteomics Urine |
| 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 | Complement proteins IgA nephropathy α-N-acetylglucosaminidase Proteomics Urine |
| url | https://peerj.com/articles/15125.pdf |
| work_keys_str_mv | AT xianiu urinarycomplementproteinsiniganephropathyprogressionfromarelativequantitativeproteomicanalysis AT shuyuzhang urinarycomplementproteinsiniganephropathyprogressionfromarelativequantitativeproteomicanalysis AT chenshao urinarycomplementproteinsiniganephropathyprogressionfromarelativequantitativeproteomicanalysis AT zhengguangguo urinarycomplementproteinsiniganephropathyprogressionfromarelativequantitativeproteomicanalysis AT jianqiangwu urinarycomplementproteinsiniganephropathyprogressionfromarelativequantitativeproteomicanalysis AT jianlingtao urinarycomplementproteinsiniganephropathyprogressionfromarelativequantitativeproteomicanalysis AT kezheng urinarycomplementproteinsiniganephropathyprogressionfromarelativequantitativeproteomicanalysis AT wenlingye urinarycomplementproteinsiniganephropathyprogressionfromarelativequantitativeproteomicanalysis AT guangyancai urinarycomplementproteinsiniganephropathyprogressionfromarelativequantitativeproteomicanalysis AT weisun urinarycomplementproteinsiniganephropathyprogressionfromarelativequantitativeproteomicanalysis AT mingxili urinarycomplementproteinsiniganephropathyprogressionfromarelativequantitativeproteomicanalysis |