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Comparative proteomic analysis of glomerular proteins in primary and bucillamine-induced membranous nephropathy

BACKGROUND: Anti-phospholipase A2 receptor autoantibody (PLA2R Ab)-associated membranous nephropathy (MN) is the most common form of primary MN (pMN). On the other hand, bucillamine (BCL), an antirheumatic drug developed in Japan, was reported to cause a rare form of secondary MN (sMN). Between thes...

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Autores principales: Kaga, Hajime, Matsumura, Hirotoshi, Suzuki, Takehiro, Dohmae, Naoshi, Odaka, Masafumi, Komatsuda, Atsushi, Takahashi, Naoto, Wakui, Hideki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281048/
https://www.ncbi.nlm.nih.gov/pubmed/35836124
http://dx.doi.org/10.1186/s12014-022-09365-x
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author Kaga, Hajime
Matsumura, Hirotoshi
Suzuki, Takehiro
Dohmae, Naoshi
Odaka, Masafumi
Komatsuda, Atsushi
Takahashi, Naoto
Wakui, Hideki
author_facet Kaga, Hajime
Matsumura, Hirotoshi
Suzuki, Takehiro
Dohmae, Naoshi
Odaka, Masafumi
Komatsuda, Atsushi
Takahashi, Naoto
Wakui, Hideki
author_sort Kaga, Hajime
collection PubMed
description BACKGROUND: Anti-phospholipase A2 receptor autoantibody (PLA2R Ab)-associated membranous nephropathy (MN) is the most common form of primary MN (pMN). On the other hand, bucillamine (BCL), an antirheumatic drug developed in Japan, was reported to cause a rare form of secondary MN (sMN). Between these MN forms, comparative proteomic analysis of glomerular proteins has not been performed. METHODS: We used renal biopsy specimens from 6 patients with PLA2R Ab (+) pMN, 6 patients with PLA2R Ab (‒) pMN, 6 patients with BCL-induced sMN, and 5 control cases (time 0 transplant biopsies). Proteins were extracted from laser-microdissected glomeruli and analyzed using mass spectrometry. The quantification values of protein abundance in each MN group were compared with those in the control group. RESULTS: More than 800 proteins with high confidence were identified. Principal component analysis revealed a different distribution between the pMN and sMN groups. For further analysis, 441 proteins matched with ≥ 3 peptides were selected. Among the pMN and sMN groups, we compared the profiles of several protein groups based on the structural and functional characteristics, such as immunoglobulins, complements, complement-regulating proteins, podocyte-associated proteins, glomerular basement membrane proteins, and several proteins that are known to be associated with kidney diseases, including MN. In all MN groups, increased levels of immunoglobulins (IgG, IgA, and IgM), complements (C3, C4, and C9), complement factor H-related protein 5, type XVIII collagen, calmodulin, polyubiquitin, and ubiquitin ligase were observed. For some proteins, such as type VII collagen and nestin, the fold-change values were significantly different between the pMN and sMN groups. CONCLUSIONS: Between the pMN and BCL-induced sMN groups, we observed common and different alterations in protein levels such as known disease-associated proteins and potential disease marker proteins. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12014-022-09365-x.
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spelling pubmed-92810482022-07-15 Comparative proteomic analysis of glomerular proteins in primary and bucillamine-induced membranous nephropathy Kaga, Hajime Matsumura, Hirotoshi Suzuki, Takehiro Dohmae, Naoshi Odaka, Masafumi Komatsuda, Atsushi Takahashi, Naoto Wakui, Hideki Clin Proteomics Research BACKGROUND: Anti-phospholipase A2 receptor autoantibody (PLA2R Ab)-associated membranous nephropathy (MN) is the most common form of primary MN (pMN). On the other hand, bucillamine (BCL), an antirheumatic drug developed in Japan, was reported to cause a rare form of secondary MN (sMN). Between these MN forms, comparative proteomic analysis of glomerular proteins has not been performed. METHODS: We used renal biopsy specimens from 6 patients with PLA2R Ab (+) pMN, 6 patients with PLA2R Ab (‒) pMN, 6 patients with BCL-induced sMN, and 5 control cases (time 0 transplant biopsies). Proteins were extracted from laser-microdissected glomeruli and analyzed using mass spectrometry. The quantification values of protein abundance in each MN group were compared with those in the control group. RESULTS: More than 800 proteins with high confidence were identified. Principal component analysis revealed a different distribution between the pMN and sMN groups. For further analysis, 441 proteins matched with ≥ 3 peptides were selected. Among the pMN and sMN groups, we compared the profiles of several protein groups based on the structural and functional characteristics, such as immunoglobulins, complements, complement-regulating proteins, podocyte-associated proteins, glomerular basement membrane proteins, and several proteins that are known to be associated with kidney diseases, including MN. In all MN groups, increased levels of immunoglobulins (IgG, IgA, and IgM), complements (C3, C4, and C9), complement factor H-related protein 5, type XVIII collagen, calmodulin, polyubiquitin, and ubiquitin ligase were observed. For some proteins, such as type VII collagen and nestin, the fold-change values were significantly different between the pMN and sMN groups. CONCLUSIONS: Between the pMN and BCL-induced sMN groups, we observed common and different alterations in protein levels such as known disease-associated proteins and potential disease marker proteins. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12014-022-09365-x. BioMed Central 2022-07-14 /pmc/articles/PMC9281048/ /pubmed/35836124 http://dx.doi.org/10.1186/s12014-022-09365-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Kaga, Hajime
Matsumura, Hirotoshi
Suzuki, Takehiro
Dohmae, Naoshi
Odaka, Masafumi
Komatsuda, Atsushi
Takahashi, Naoto
Wakui, Hideki
Comparative proteomic analysis of glomerular proteins in primary and bucillamine-induced membranous nephropathy
title Comparative proteomic analysis of glomerular proteins in primary and bucillamine-induced membranous nephropathy
title_full Comparative proteomic analysis of glomerular proteins in primary and bucillamine-induced membranous nephropathy
title_fullStr Comparative proteomic analysis of glomerular proteins in primary and bucillamine-induced membranous nephropathy
title_full_unstemmed Comparative proteomic analysis of glomerular proteins in primary and bucillamine-induced membranous nephropathy
title_short Comparative proteomic analysis of glomerular proteins in primary and bucillamine-induced membranous nephropathy
title_sort comparative proteomic analysis of glomerular proteins in primary and bucillamine-induced membranous nephropathy
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281048/
https://www.ncbi.nlm.nih.gov/pubmed/35836124
http://dx.doi.org/10.1186/s12014-022-09365-x
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