Characterization of diabetic nephropathy in CaM kinase IIα (Thr286Asp) transgenic mice

Hikari Suzuki, Ichiro Kato, Isao Usui, Ichiro Takasaki, Yoshiaki Tabuchi, Takeshi Oya, Koichi Tsuneyama, Hiroshi Kawaguchi, Koichi Hiraga, Shin Takasawa, Hiroshi Okamoto, Kazuyuki Tobe, Masakiyo Sasahara

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Detailed studies were performed on diabetic kidneys derived from transgenic mice overexpressing the mutant form (Thr286Asp) of Ca2+/calmodulin-dependent protein kinase IIα (CaM kinase IIα) in pancreatic β-cells. Kidney weight/body weight ratio, urinary albumin/creatinine ratio, serum BUN level, and mesangial/glomerular area ratio were all significantly higher in transgenic mice than in wild-type mice. cDNA microarray analysis revealed 17 up-regulated genes and 12 down-regulated genes in transgenic kidney. Among up-regulated genes, cyclin D2 (6.70-fold) and osteopontin (2.35-fold) were thought to play important roles in the progression of diabetic nephropathy. Transgenic glomeruli and tubular epithelial cells were strongly stained for osteopontin, a molecule which induces immune response. In quantitative real-time RT-PCR analyses, expressions of not only M1 macrophage marker genes but also M2 macrophage marker genes were elevated in renal cortex of transgenic mice. Overall results indicate that CaM kinase IIα (Thr286Asp) transgenic mice serve as an excellent model for diabetic nephropathy.

Original languageEnglish
Pages (from-to)38-42
Number of pages5
JournalBiochemical and biophysical research communications
Volume379
Issue number1
DOIs
Publication statusPublished - 2009 Jan 30

Keywords

  • Ca/calmodulin-dependent protein kinase II
  • Cyclin D2
  • Diabetes
  • Macrophage
  • Nephropathy
  • Osteopontin
  • Transgenic mice
  • cDNA microarray

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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