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

doi:10.1016/j.bbrc.2008.11.143

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

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研究成果: ジャーナルへの寄稿 › 学術論文 › 査読

4 被引用数 (Scopus)

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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.

本文言語	英語
ページ（範囲）	38-42
ページ数	5
ジャーナル	Biochemical and Biophysical Research Communications
巻	379
号	1
DOI	https://doi.org/10.1016/j.bbrc.2008.11.143
出版ステータス	出版済み - 2009/01/30

ASJC Scopus 主題領域

生物理学
生化学
分子生物学
細胞生物学

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10.1016/j.bbrc.2008.11.143

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title = "Characterization of diabetic nephropathy in CaM kinase IIα (Thr286Asp) transgenic mice",

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.",

keywords = "Ca/calmodulin-dependent protein kinase II, Cyclin D2, Diabetes, Macrophage, Nephropathy, Osteopontin, Transgenic mice, cDNA microarray",

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

year = "2009",

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doi = "10.1016/j.bbrc.2008.11.143",

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T1 - Characterization of diabetic nephropathy in CaM kinase IIα (Thr286Asp) transgenic mice

AU - Suzuki, Hikari

AU - Kato, Ichiro

AU - Usui, Isao

AU - Takasaki, Ichiro

AU - Tabuchi, Yoshiaki

AU - Oya, Takeshi

AU - Tsuneyama, Koichi

AU - Kawaguchi, Hiroshi

AU - Hiraga, Koichi

AU - Takasawa, Shin

AU - Okamoto, Hiroshi

AU - Tobe, Kazuyuki

AU - Sasahara, Masakiyo

PY - 2009/1/30

Y1 - 2009/1/30

N2 - 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.

AB - 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.

KW - Ca/calmodulin-dependent protein kinase II

KW - Cyclin D2

KW - Diabetes

KW - Macrophage

KW - Nephropathy

KW - Osteopontin

KW - Transgenic mice

KW - cDNA microarray

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

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