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논문분류	춘계학술대회 초록집
제목	Multi-sample mass spectrometry-based approach for discovering injury markers in chronic kidney disease
저자	Ji Eun Kim, Dohyun Han, Sunhwa Lee, Yong Chul Kim, Kyung Don Yoo, Jae Wook Lee, Dong Ki Kim, Young Joo Kwon, Yon Su Kim, Seung Hee Yang
출판정보	2020; 2020(1):
키워드	chronic kidney disease \| mass spectrometry \| proteomics \| fibrosis \| LGALS-1
초록	Urinary proteomics studies have primarily focused on identifying markers of chronic kidney disease (CKD) progression. Here, we aimed to specify CKD-related injury markers through proteomics analysis in animal kidney tissues and cells, along with urine of patients with CKD. Label-free quantitative proteomics analysis based on liquid chromatography-tandem mass spectrometry was performed on urine samples obtained from 9, 11, and 10 patients in CKD stage 1, 3 and 5, respectively, and 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) before and after inducing 24-h hypoxia injury. Proteins commonly identified across the three sample types were validated. Upon hierarchical clustering, 264 among 2577 proteins in CKD urine increased sequentially according to CKD stage. Between rat 5/6 nephrectomized and sham-operated kidney tissue, 2497 proteins differed significantly; 4032 significantly differed between human GECs under normoxic and hypoxic conditions. Overall, five proteins (galectin-1, protein S, thymosin beta-4, gelsolin, and vimentin) increased with chronic injury in all types of samples. Among the five proteins, the validation analyses for protein S and galectin-1 were performed and galectin-1 showed significant inverse correlation with renal function as well as higher expression in glomerulus with chronic injury compared to protein S. After blocking Galectin-1, anti-fibrotic and anti-apoptotic effect was discovered in hypoxia induced fibrosis injury. This constitutes the first multi-sample proteomics study for identifying key renal-expressed proteins associated CKD progression. The discovered proteins represent potential markers of chronic renal cell and tissue damage, and candidates for contributing to CKD pathophysiology.
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