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Nephrol Dial Transplant. 2013 Oct;28(10):2477-83. doi: 10.1093/ndt/gft308.

Krüppel-like factor 5 associates with melamine-cyanurate crystal-induced nephritis in rats.

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  • 1Department and Institute of Physiology, National Yang-Ming University, Taipei, Taiwan.

Abstract

BACKGROUND:

Melamine and cyanuric acid (M/CA), when orally administered together to rats, can induce crystal formation within renal tubules and cause acute kidney injury.

METHODS:

To investigate the pathomechanism of crystal-induced nephritis, melamine and/or cyanuric acid were administered to 3-week-old (young) and 8-week-old (adult) rats, respectively.

RESULTS:

Crystal formation, blood urea nitrogen elevation, tubular cell injury and macrophage infiltration were noted in rats fed with M/CA, but not in rats fed with vehicle, melamine or CA alone. These parameters were significantly higher in young rats than those in adult rats fed with M/CA 200 mg/kg body weight (BW) for 3 days. Krüppel-like factor 5 (KLF5) was expressed on distal tubule cells, especially when crystals deposited within the lumens. Both mRNA and protein levels were higher in young rats than those in adult rats fed with M/CA (200 mg/kg BW). KLF5 expression has been shown to modulate renal tissue cytokine production, and we found that proinflammatory cytokines like monocyte chemoattractant protein-1 and interlukin-6 were increased in kidney tissues of young rats fed with M/CA for 3 days. In contrast, interlukin-10, an anti-inflammatory cytokine, was upregulated in kidneys of adult rats fed with M/CA for 3 days.

CONCLUSIONS:

Crystals are prone to deposition in distal tubules of young rats fed with M/CA. M/CA Crystal-related nephritis might be induced by the KLF5 expression, which modulated macrophage recruitment and proinflammatory cytokine production, subsequently leading to renal tubular injury and interstitial inflammation.

KEYWORDS:

crystal formation; cyanuric acid; krüppel-like factor 5; macrophage; melamine

PMID:
24078640
[PubMed - indexed for MEDLINE]
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