CD-1(db/db) mice: A novel type 2 diabetic mouse model with progressive kidney fibrosis.
CD-1(db/db) mice: A novel type 2 diabetic mouse model with progressive kidney fibrosis.
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CD-1（DB/DB）小鼠：一种具有进行性肾脏纤维化的新型2型糖尿病小鼠模型。
DOI：
10.1111/jdi.13311
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发表时间：
2020-11
影响因子：
3.2
通讯作者：
Koya D
中科院分区：
文献类型：
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作者：
Mizunuma Y;Kanasaki K;Nitta K;Nakamura Y;Ishigaki Y;Takagaki Y;Kitada M;Li S;Liu H;Li J;Usui I;Aso Y;Koya D
为了建立对抗糖尿病肾病的新疗法，人类疾病相关动物模型至关重要。然而，尚未建立表现出进行性肾纤维化的2型糖尿病小鼠模型。与抗纤维化肽N-乙酰-丝氨酰-赖氨酰-脯氨酸抑制相关的其他背景小鼠相比，链脲佐菌素诱导的糖尿病CD-1小鼠的肾脏显示出严重的纤维化。BKS背景（BKSdb / db）常用于糖尿病肾病研究; BKSdb / db表型中的肾纤维化极轻微。我们通过将db基因回交到CD-1背景中来产生CD-1db / db小鼠，并与BKSdb / db和CD-1db / m小鼠相比分析表型差异。与BKSdb / db小鼠相比，雄性CD-1db / db小鼠的血糖水平似乎升高。CD-1db / db小鼠的空腹胰岛素水平下降。16 - 24周龄CD-1db / db小鼠的血浆胱抑素C水平有升高趋势。与年龄匹配的BKSdb /db小鼠相比，雄性CD-1db / db小鼠在16至24周龄期间显示出显著的进行性肾脏和心脏纤维化。基因表达谱显示雄性CD-1db / db小鼠中的纤维化程序相关基因。与BKSdb / db相比，24周龄雄性CD-1db / db小鼠的尿液抗纤维化肽N-乙酰基-丝氨酰-天冬氨酰-赖氨酰-脯氨酸显着降低。CD-1小鼠中脯氨酰寡肽酶（从胸腺素β4产生抗纤维化肽N-乙酰-丝氨酰-乙酰-赖氨酰-脯氨酸所必需的酶）的基因表达显著较低。CD-1小鼠的胸腺素β4水平也较低。这些结果表明，CD-1db / db小鼠是一种新的2型糖尿病小鼠模型，具有进行性肾脏和心脏纤维化。为了建立糖尿病肾病的治疗方法，人类疾病相关的动物模型是必不可少的。尚未建立表现出进行性肾纤维化的2型糖尿病小鼠模型。在这项研究中，我们产生了CD-1db / db小鼠，这是一种新的2型糖尿病小鼠模型，具有糖尿病肾病（包括肾纤维化）的进行性表型。
To establish novel therapies to combat diabetic kidney disease, a human disease‐relevant animal model is essential. However, a type 2 diabetic mouse model presenting progressive kidney fibrosis has not yet been established. Kidneys of streptozotocin‐induced diabetic CD‐1 mice showed severe fibrosis compared with other backgrounds of mice associated with the suppression of antifibrotic peptide N‐acetyl‐seryl‐aspartyl‐lysyl‐proline. The BKS background (BKSdb / db) is often utilized for diabetic kidney disease research; the kidney fibrosis in the BKSdb / db phenotype is minimal. We generated CD‐1db / db mice by backcrossing the db gene into the CD‐1 background, and analyzed phenotypic differences compared with BKSdb / db and CD‐1db / m mice. Male CD‐1db / db mice appeared to have elevated blood glucose levels compared with those of BKSdb / db mice. Fasting insulin levels declined in CD‐1db / db mice. Plasma cystatin C levels tended to be elevated in CD‐1db / db mice from 16 to 24 weeks‐of‐age. Male CD‐1db / db mice showed significantly progressive kidney and heart fibrosis from 16 to 24 weeks‐of‐age when compared with that of age‐matched BKSdb / db mice. The gene expression profile showed fibrogenic program‐associated genes in male CD‐1db / db mice. Male CD‐1db / db mice displayed significantly lower urine antifibrotic peptide N‐acetyl‐seryl‐aspartyl‐lysyl‐proline when compared to that of BKSdb / db at 24 weeks‐of‐age. The gene expression of prolyl oligopeptidase, the enzyme essential for antifibrotic peptide N‐acetyl‐seryl‐aspartyl‐lysyl‐proline production from thymosin β4, was significantly lower in the CD‐1 mice. Thymosin β4 levels were also lower in CD‐1 mice. These results suggest that CD‐1db / db mice are a novel type 2 diabetic mouse model with progressive kidney and heart fibrosis. To establish therapies for diabetic kidney disease, a human disease‐relevant animal model is essential. A type 2 diabetic mouse model presenting progressive kidney fibrosis has not yet been established. In this study, we generated CD‐1db / db mice, which are a novel type 2 diabetic mouse model with a progressive phenotype of diabetic kidney disease including kidney fibrosis.
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影响因子：
--
作者：
Nagai T;Kanasaki M;Srivastava SP;Nakamura Y;Ishigaki Y;Kitada M;Shi S;Kanasaki K;Koya D
通讯作者：
Koya D
影响因子：
4.2
作者：
Castoldi, G.;di Gioia, C. R. T.;Stella, A.
通讯作者：
Stella, A.
影响因子：
3.5
作者：
GRILLON, C;RIEGER, K;LENFANT, M
通讯作者：
LENFANT, M
抗纤维化 MicroRNA 串扰对 N-乙酰基-丝氨酰-天冬氨酰-赖氨酰-脯氨酸在糖尿病相关肾纤维化中作用的影响。
影响因子：
4.6
作者：
Srivastava SP;Shi S;Kanasaki M;Nagai T;Kitada M;He J;Nakamura Y;Ishigaki Y;Kanasaki K;Koya D
通讯作者：
Koya D
DOI：
10.1007/s10162-002-3026-6
发表时间：
2003-09-01
影响因子：
2.4
作者：
Wu, T;Marcus, DC
通讯作者：
Marcus, DC