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Nephron Exp Nephrol. 2007;107(1):e12-21. Epub 2007 Jul 18.

Blockade of IP-10/CXCR3 promotes progressive renal fibrosis.

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  • 1Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.

Abstract

BACKGROUND/AIM:

Fibrosis is a hallmark of progressive organ disease. The 10-kDa interferon-inducible protein IP-10/CXCL10 is a potent chemoattractant for activated T lymphocytes, natural killer cells, and monocytes. However, the involvement of IP-10 in the pathogenesis of renal diseases via its receptor, CXCR3, remains unclear. To contribute to the clarification of this issue was the aim of this study.

METHODS:

The impacts of IP-10 on renal fibrosis were investigated in a unilateral ureteral obstruction model in CXCR3-deficient mice and mice treated with anti-IP-10-neutralizing monoclonal antibody. Anti-IP-10 monoclonal antibody (5 mg/kg/day) was injected intravenously once a day until sacrifice on days 1, 4, or 7 after treatment. The effects of IP-10 were confirmed in cultured tubular epithelial cells.

RESULTS:

IP-10 and CXCR3 were upregulated in progressive renal fibrosis. Blockade of IP-10/CXCR3 promotes renal fibrosis, as evidenced by increases in interstitial fibrosis and hydroxyproline contents, concomitant decrease in hepatocyte growth factor expression, and converse increase in transforming growth factor-beta1 in diseased kidneys. IP-10 blockade affected neither macrophage nor T cell infiltration in diseased kidneys.

CONCLUSION:

These results suggest that blockade of IP-10 via CXCR3 contributes to renal fibrosis, possibly by upregulation of transforming growth factor-beta1, concomitant with downregulation of hepatocyte growth factor.

Copyright 2007 S. Karger AG, Basel.

PMID:
17671396
[PubMed - indexed for MEDLINE]
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