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Title: Molecular markers of tubulointerstitial fibrosis and tubular cell damage in patients with chronic kidney disease
Authors: Nakagawa, Shunsaku  kyouindb  KAKEN_id
Nishihara, Kumiko
Miyata, Hitomi
Shinke, Haruka
Tomita, Eri
Kajiwara, Moto
Matsubara, Takeshi
Iehara, Noriyuki
Igarashi, Yoshinobu
Yamada, Hiroshi
Fukatsu, Atsushi
Yanagita, Motoko  kyouindb  KAKEN_id
Matsubara, Kazuo  kyouindb  KAKEN_id
Masuda, Satohiro
Author's alias: 中山, 俊作
宮田, 仁美
松原, 雄
柳田, 素子
松原, 和夫
Issue Date: 28-Aug-2015
Publisher: Public Library of Science
Journal title: PLOS ONE
Volume: 10
Issue: 8
Thesis number: e0136994
Abstract: In chronic kidney disease (CKD), progressive nephron loss causes glomerular sclerosis, as well as tubulointerstitial fibrosis and progressive tubular injury. In this study, we aimed to identify molecular changes that reflected the histopathological progression of renal tubulointerstitial fibrosis and tubular cell damage. A discovery set of renal biopsies were obtained from 48 patients with histopathologically confirmed CKD, and gene expression profiles were determined by microarray analysis. The results indicated that hepatitis A virus cellular receptor 1 (also known as Kidney Injury Molecule-1, KIM-1), lipocalin 2 (also known as neutrophil gelatinase-associated lipocalin, NGAL), SRY-box 9, WAP four-disulfide core domain 2, and NK6 homeobox 2 were differentially expressed in CKD. Their expression levels correlated with the extent of tubulointerstitial fibrosis and tubular cell injury, determined by histopathological examination. The expression of these 5 genes was also increased as kidney damage progressed in a rodent unilateral ureteral obstruction model of CKD. We calculated a molecular score using the microarray gene expression profiles of the biopsy specimens. The composite area under the receiver operating characteristics curve plotted using this molecular score showed a high accuracy for diagnosing tubulointerstitial fibrosis and tubular cell damage. The robust sensitivity of this score was confirmed in a validation set of 5 individuals with CKD. These findings identified novel molecular markers with the potential to contribute to the detection of tubular cell damage and tubulointerstitial fibrosis in the kidney.
Rights: © 2015 Nakagawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
DOI(Published Version): 10.1371/journal.pone.0136994
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