Urinary chemokine (C-C motif) ligand 2 (monocyte chemotactic protein-1) as a tubular injury marker for early detection of cisplatin-induced nephrotoxicity

Kumiko Nishihara, Satohiro Masuda, Haruka Shinke, Aiko Ozawa, Takaharu Ichimura, Atsushi Yonezawa, Shunsaku Nakagawa, Ken Ichi Inui, Joseph V. Bonventre, Kazuo Matsubara

Research output: Contribution to journalArticle

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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 (5 mg/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 (2 mg/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.

Original languageEnglish
Pages (from-to)570-582
Number of pages13
JournalBiochemical Pharmacology
Volume85
Issue number4
DOIs
Publication statusPublished - Feb 15 2013
Externally publishedYes

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Chemokine CCL2
Cisplatin
Wounds and Injuries
Kidney
Chemokines
Messenger RNA
Molecules
Rats
Chemokine CXCL1
Cytokines
Proximal Kidney Tubule
Blood Urea Nitrogen
Microarray Analysis
Microarrays
Interleukin-1beta
Acute Kidney Injury
Chronic Kidney Failure
Fluorescent Antibody Technique
Deterioration
Urea

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Biochemistry

Cite this

Urinary chemokine (C-C motif) ligand 2 (monocyte chemotactic protein-1) as a tubular injury marker for early detection of cisplatin-induced nephrotoxicity. / Nishihara, Kumiko; Masuda, Satohiro; Shinke, Haruka; Ozawa, Aiko; Ichimura, Takaharu; Yonezawa, Atsushi; Nakagawa, Shunsaku; Inui, Ken Ichi; Bonventre, Joseph V.; Matsubara, Kazuo.

In: Biochemical Pharmacology, Vol. 85, No. 4, 15.02.2013, p. 570-582.

Research output: Contribution to journalArticle

Nishihara, K, Masuda, S, Shinke, H, Ozawa, A, Ichimura, T, Yonezawa, A, Nakagawa, S, Inui, KI, Bonventre, JV & Matsubara, K 2013, 'Urinary chemokine (C-C motif) ligand 2 (monocyte chemotactic protein-1) as a tubular injury marker for early detection of cisplatin-induced nephrotoxicity', Biochemical Pharmacology, vol. 85, no. 4, pp. 570-582. https://doi.org/10.1016/j.bcp.2012.12.019
Nishihara, Kumiko ; Masuda, Satohiro ; Shinke, Haruka ; Ozawa, Aiko ; Ichimura, Takaharu ; Yonezawa, Atsushi ; Nakagawa, Shunsaku ; Inui, Ken Ichi ; Bonventre, Joseph V. ; Matsubara, Kazuo. / Urinary chemokine (C-C motif) ligand 2 (monocyte chemotactic protein-1) as a tubular injury marker for early detection of cisplatin-induced nephrotoxicity. In: Biochemical Pharmacology. 2013 ; Vol. 85, No. 4. pp. 570-582.
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AU - Ichimura, Takaharu

AU - Yonezawa, Atsushi

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