Krüppel-like factor 5 associates with melamine-cyanurate crystal-induced nephritis in rats.
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.
Department and Institute of Physiology, National Yang-Ming University, Taipei, Taiwan.
Hsin-Lei
HL
Huang
Wen-Ying
WY
Yang
Hsiao-Fung
HF
Pu
Tung-Hu
TH
Tsai
Chi-Hung
CH
Lin
Nien-Jung
NJ
Chen
Der-Cherng
DC
Tarng
D000818:Animals; D015153:Blotting, Western; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D007684:Kidney Tubules / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009393:Nephritis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012117:Resins, Synthetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014227:Triazines / Q000633:toxicity*
C492215:Klf5 protein, rat; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; D012117:Resins, Synthetic; D014227:Triazines; C004632:cyanuric acid; C011907:melamine
crystal formation; cyanuric acid; krüppel-like factor 5; macrophage; melamine