KLI

Multi-sample mass spectrometry-based approach for discovering injury markers in chronic kidney disease

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Abstract
Urinary proteomics studies have primarily focused on identifying markers of chronic kidney
disease (CKD) progression. Here, we aimed to determine urinary markers of CKD renal
parenchymal injury through proteomics analysis in animal kidney tissues and cells and in the
urine of patients with CKD. Label-free quantitative proteomics analysis based on liquid
chromatography-tandem mass spectrometry was performed on urine samples obtained from 6
normal controls and 9, 11, and 10 patients with CKD stages 1, 3, and 5, respectively, and on
kidney tissue samples from a rat CKD model by 5/6 nephrectomy. Tandem mass tag-based
quantitative proteomics analysis was performed for primary cultured glomerular endothelial
cells (GECs) and proximal tubular epithelial cells (PTECs) before and after inducing 24-h
hypoxia injury. Upon hierarchical clustering, out of 858 differentially expressed proteins
(DEPs) in the urine of CKD patients, the levels of 416 decreased and 403 increased
sequentially according to the disease stage, respectively. Among 2965 DEPs across 5/6
nephrectomized and sham-operated rat kidney tissues, 86 DEPs showed same expression
patterns in the urine and kidney tissue. After cross-validation with two external animal
proteome datasets, 38 DEPs were organized; only 10 DEPs, including serotransferrin,
gelsolin, poly ADP-ribose polymerase 1, neuroblast differentiation-associated protein
AHNAK, microtubule-associated protein 4, galectin-1, protein S, thymosin beta-4,
myristoylated alanine-rich C-kinase substrate, and vimentin were finalized by screening
human GECs and PTECs data. Among these ten potential candidates for universal CKD
marker, validation analyses for protein S and galectin-1 were conducted. Galectin-1 was
observed to have a significant inverse correlation with renal function as well as higher
expression in glomerulus with chronic injury than protein S. This constitutes the first multisample
proteomics study for identifying key renal-expressed proteins associated with CKD
Author(s)
권영주김동기김연수김용철김지은문종주문현경양승희유경돈이선화이재욱정진선한도현
Issued Date
2021
Type
Article
Keyword
울산의대 미표기 반려
DOI
10.1074/mcp.RA120.002159
URI
https://oak.ulsan.ac.kr/handle/2021.oak/7025
Publisher
MOLECULAR & CELLULAR PROTEOMICS
Location
미국
Language
한국어
ISSN
1535-9476
Citation Volume
20
Citation Start Page
100037
Citation End Page
100037
Appears in Collections:
Medicine > Medicine
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