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

Hsin Lei Huang, Wen Ying Yang, Hsiao Fung Pu, Tung Hu Tsai, Chi Hung Lin, Nien Jung Chen, Der Cherng Tarng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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

Original languageEnglish
Pages (from-to)2477-2483
Number of pages7
JournalNephrology Dialysis Transplantation
Volume28
Issue number10
DOIs
StatePublished - Oct 2013

Keywords

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

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