Urinary peptidomics reveals proteases involved in idiopathic membranous nephropathy

Abstract Background Idiopathic membranous nephropathy (IMN) is a cause of nephrotic syndrome that is increasing in incidence but has unclear pathogenesis. Urinary peptidomics is a promising technology for elucidating molecular mechanisms underlying diseases. Dysregulation of the proteolytic system i...

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Main Authors: Baoxu Lin, Jianhua Liu, Yue Zhang, Yabin Wu, Shixiao Chen, Yibo Bai, Qiuying Liu, Xiaosong Qin
Format: Article
Language:English
Published: BMC 2021-11-01
Series:BMC Genomics
Subjects:
Online Access:https://doi.org/10.1186/s12864-021-08155-3
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author Baoxu Lin
Jianhua Liu
Yue Zhang
Yabin Wu
Shixiao Chen
Yibo Bai
Qiuying Liu
Xiaosong Qin
author_facet Baoxu Lin
Jianhua Liu
Yue Zhang
Yabin Wu
Shixiao Chen
Yibo Bai
Qiuying Liu
Xiaosong Qin
author_sort Baoxu Lin
collection DOAJ
description Abstract Background Idiopathic membranous nephropathy (IMN) is a cause of nephrotic syndrome that is increasing in incidence but has unclear pathogenesis. Urinary peptidomics is a promising technology for elucidating molecular mechanisms underlying diseases. Dysregulation of the proteolytic system is implicated in various diseases. Here, we aimed to conduct urinary peptidomics to identify IMN-related proteases. Results Peptide fingerprints indicated differences in naturally produced urinary peptide components among 20 healthy individuals, 22 patients with IMN, and 15 patients with other kidney diseases. In total, 1,080 peptide-matched proteins were identified, 279 proteins differentially expressed in the urine of IMN patients were screened, and 32 proteases were predicted; 55 of the matched proteins were also differentially expressed in the kidney tissues of IMN patients, and these were mainly involved in the regulation of proteasome-, lysosome-, and actin cytoskeleton-related signaling pathways. The 32 predicted proteases showed abnormal expression in the glomeruli of IMN patients based on Gene Expression Omnibus databases. Western blot revealed abnormal expression of calpain, matrix metalloproteinase 14, and cathepsin S in kidney tissues of patients with IMN. Conclusions This work shown the calpain/matrix metalloproteinase/cathepsin axis might be dysregulated in IMN. Our study is the first to systematically explore the role of proteases in IMN by urinary peptidomics, which are expected to facilitate discovery of better biomarkers for IMN.
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spelling doaj.art-304b1ce3c3e740239e3d34ff25cd62ed2022-12-21T21:25:00ZengBMCBMC Genomics1471-21642021-11-0122111210.1186/s12864-021-08155-3Urinary peptidomics reveals proteases involved in idiopathic membranous nephropathyBaoxu Lin0Jianhua Liu1Yue Zhang2Yabin Wu3Shixiao Chen4Yibo Bai5Qiuying Liu6Xiaosong Qin7Department of Laboratory Medicine, Shengjing Hospital of China Medical UniversityDepartment of Laboratory Medicine, Shengjing Hospital of China Medical UniversityDepartment of Laboratory Medicine, Shengjing Hospital of China Medical UniversityDepartment of Laboratory Medicine, Shengjing Hospital of China Medical UniversityDepartment of Laboratory Medicine, Shengjing Hospital of China Medical UniversityDepartment of Laboratory Medicine, Shengjing Hospital of China Medical UniversityDepartment of Laboratory Medicine, Shengjing Hospital of China Medical UniversityDepartment of Laboratory Medicine, Shengjing Hospital of China Medical UniversityAbstract Background Idiopathic membranous nephropathy (IMN) is a cause of nephrotic syndrome that is increasing in incidence but has unclear pathogenesis. Urinary peptidomics is a promising technology for elucidating molecular mechanisms underlying diseases. Dysregulation of the proteolytic system is implicated in various diseases. Here, we aimed to conduct urinary peptidomics to identify IMN-related proteases. Results Peptide fingerprints indicated differences in naturally produced urinary peptide components among 20 healthy individuals, 22 patients with IMN, and 15 patients with other kidney diseases. In total, 1,080 peptide-matched proteins were identified, 279 proteins differentially expressed in the urine of IMN patients were screened, and 32 proteases were predicted; 55 of the matched proteins were also differentially expressed in the kidney tissues of IMN patients, and these were mainly involved in the regulation of proteasome-, lysosome-, and actin cytoskeleton-related signaling pathways. The 32 predicted proteases showed abnormal expression in the glomeruli of IMN patients based on Gene Expression Omnibus databases. Western blot revealed abnormal expression of calpain, matrix metalloproteinase 14, and cathepsin S in kidney tissues of patients with IMN. Conclusions This work shown the calpain/matrix metalloproteinase/cathepsin axis might be dysregulated in IMN. Our study is the first to systematically explore the role of proteases in IMN by urinary peptidomics, which are expected to facilitate discovery of better biomarkers for IMN.https://doi.org/10.1186/s12864-021-08155-3Urinary peptidomicsIdiopathic membranous nephropathyProteases
spellingShingle Baoxu Lin
Jianhua Liu
Yue Zhang
Yabin Wu
Shixiao Chen
Yibo Bai
Qiuying Liu
Xiaosong Qin
Urinary peptidomics reveals proteases involved in idiopathic membranous nephropathy
BMC Genomics
Urinary peptidomics
Idiopathic membranous nephropathy
Proteases
title Urinary peptidomics reveals proteases involved in idiopathic membranous nephropathy
title_full Urinary peptidomics reveals proteases involved in idiopathic membranous nephropathy
title_fullStr Urinary peptidomics reveals proteases involved in idiopathic membranous nephropathy
title_full_unstemmed Urinary peptidomics reveals proteases involved in idiopathic membranous nephropathy
title_short Urinary peptidomics reveals proteases involved in idiopathic membranous nephropathy
title_sort urinary peptidomics reveals proteases involved in idiopathic membranous nephropathy
topic Urinary peptidomics
Idiopathic membranous nephropathy
Proteases
url https://doi.org/10.1186/s12864-021-08155-3
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