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Title: Urinary chemokine (C-C motif) ligand 2 (monocyte chemotactic protein-1) as a tubular injury marker for early detection of cisplatin-induced nephrotoxicity.
Authors: Nishihara, Kumiko
Masuda, Satohiro
Shinke, Haruka
Ozawa, Aiko
Ichimura, Takaharu
Yonezawa, Atsushi  kyouindb  KAKEN_id  orcid (unconfirmed)
Nakagawa, Shunsaku  kyouindb  KAKEN_id
Inui, Ken-Ichi
Bonventre, Joseph V
Matsubara, Kazuo  kyouindb  KAKEN_id
Author's alias: 増田, 智先
Keywords: Acute kidney injury
Microarray analysis
Renal proximal tubule cells
Monocyte chemotactic protein-1
Kidney injury molecule-1
Issue Date: 15-Feb-2013
Publisher: Elsevier Inc.
Journal title: Biochemical pharmacology
Volume: 85
Issue: 4
Start page: 570
End page: 582
Abstract: Because of the difficulty in detecting segment-specific response in the kidney, we investigated the molecular events underlying acute kidney injury in the proximal tubules of rats with cisplatin (cis-diamminedichloroplatinum II)-induced nephrotoxicity. Microarray analysis revealed that mRNA levels of several cytokines and chemokines, such as interleukin-1beta, chemokine (C-C motif) ligand (CCL) 2, CCL20, chemokine (C-X-C motif) ligand (CXCL) 1, and CXCL10 were significantly increased after cisplatin treatment in both isolated proximal tubules and whole kidney. Interestingly, tubular CCL2 mRNA levels increased soon after cisplatin administration, whereas CCL2 mRNA levels in whole kidney first decreased and then increased. Levels of both CCL2 and kidney injury molecule-1 (KIM-1) in the whole kidney increased after cisplatin administration. Immunofluorescence analysis revealed CCL2 changes in the proximal tubular cells initially and then in the medullary interstitium. Urinary CCL2 excretion significantly increased approximately 3-fold compared with controls the day after cisplatin administration (5mg/kg), when no changes were observed plasma creatinine and blood urea nitrogen levels. Urinary levels of KIM-1 also increased 3-fold after cisplatin administration. In addition, urinary CCL2 rather than KIM-1 increased in chronic renal failure rats after administration of low-dose cisplatin (2mg/kg), suggesting that urinary CCL2 was selective for cisplatin-induced nephrotoxicity in renal impairment. These results indicated that the increase in cytokine and chemokine expression in renal epithelial cells might be responsible for kidney deterioration in cisplatin-induced nephrotoxicity, and that urinary CCL2 is associated with tubular injury and serves as a sensitive and noninvasive marker for the early detection of cisplatin-induced tubular injury.
Rights: © 2012 Elsevier Inc.
この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。This is not the published version. Please cite only the published version.
DOI(Published Version): 10.1016/j.bcp.2012.12.019
PubMed ID: 23291264
Appears in Collections:Journal Articles

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