title: A kidney injury molecule-1 (Kim-1) gene reporter in a mouse artificial chromosome: the responsiveness to cisplatin toxicity in immortalized mouse kidney S3 cells.
abstract: BACKGROUND
  Kidney injury molecule-1 (Kim-1) has been validated as a urinary biomarker for acute and chronic renal damage. The expression of Kim-1 mRNA is also activated by acute kidney injury induced by cisplatin in rodents and humans. To date, the measurement of Kim-1 expression has not fully allowed the detection of in vitro cisplatin nephrotoxicity in immortalized culture cells, such as human kidney-2 cells and immortalized proximal tubular epithelial cells.
  
  
  METHODS
  We measured the augmentation of Kim-1 mRNA expression after the addition of cisplatin using immortalized S3 cells established from the kidneys of transgenic mice harboring temperature-sensitive large T antigen from Simian virus 40.
  
  
  RESULTS
  A mouse Kim-1 gene luciferase reporter in conjunction with an Hprt gene reporter detected cisplatin-induced nephrotoxicity in S3 cells. These two reporter genes were contained in a mouse artificial chromosome, and two luciferases that emitted different wavelengths were used to monitor the respective gene expression. However, the Kim-1 reporter gene failed to respond to cisplatin in A9 fibroblast cells that contained the same reporter mouse artificial chromosome, suggesting cell type-specificity for activation of the reporter.
  
  
  CONCLUSIONS
  We report the feasibility of measuring in vitro cisplatin nephrotoxicity using a Kim-1 reporter gene in S3 cells.
authors: Chromosome Engineering Research Center (CERC), Tottori University, Tottori, Japan.|Division of Human Genome Science, Department of Molecular and Cellular Biology, School of Life Sciences, Faculty of Medicine, Tottori University, Tottori, Japan.
authors: Kenji
authors: http://orcid.org/0000-0001-6616-2270
authors: K
authors: Kokura
authors: Tottori Industrial Promotion Organization, Tottori, Tottori, Japan.|Division of Laboratory Animal Science, Research Center for Bioscience and Technology, Tottori University, Tottori, Japan.
authors: Yasushi
authors: Y
authors: Kuromi
authors: Tottori Industrial Promotion Organization, Tottori, Tottori, Japan.
authors: Takeshi
authors: T
authors: Endo
authors: Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Tochigi, Japan.|Department of Pharmacology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors: Naohiko
authors: N
authors: Anzai
authors: Chromosome Engineering Research Center (CERC), Tottori University, Tottori, Japan.
authors: Yasuhiro
authors: Y
authors: Kazuki
authors: Chromosome Engineering Research Center (CERC), Tottori University, Tottori, Japan.
authors: Mitsuo
authors: M
authors: Oshimura
authors: Tottori Industrial Promotion Organization, Tottori, Tottori, Japan. ohbayashi@grape.med.tottori-u.ac.jp.
authors: Tetsuya
authors: T
authors: Ohbayashi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D022201:Chromosomes, Artificial / Q000235:genetics*; D002945:Cisplatin / Q000633:toxicity; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D017930:Genes, Reporter / Q000235:genetics*; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000235:genetics* / Q000378:metabolism; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008822:Mice, Transgenic
chemical_list: D000970:Antineoplastic Agents; C442240:Havcr1 protein, mouse; D000072596:Hepatitis A Virus Cellular Receptor 1; D008156:Luciferases; D007041:Hypoxanthine Phosphoribosyltransferase; D002945:Cisplatin
keywords: Kim-1; S3 cells; cisplatin; mouse artificial chromosome; nephrotoxicity; reporter gene