Diabetic kidney disease in FVB/NJ Akita mice: temporal pattern of kidney injury and urinary nephrin excretion.
Diabetic kidney disease in FVB/NJ Akita mice: temporal pattern of kidney injury and urinary nephrin excretion.
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DOI：
10.1371/journal.pone.0033942
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Spurney RF
中科院分区：
文献类型：
--
作者：
Chang JH;Paik SY;Mao L;Eisner W;Flannery PJ;Wang L;Tang Y;Mattocks N;Hadjadj S;Goujon JM;Ruiz P;Gurley SB;Spurney RF
秋田小鼠是1型糖尿病的遗传模型。在本研究中，我们研究了FVB/NJ背景下的秋田小鼠的表型，并检查了尿nephrin排泄作为肾损伤的标志物。将雄性秋田小鼠与非糖尿病对照小鼠的肾脏和心脏疾病的功能和结构特征进行比较。检测两组大鼠足细胞数量、凋亡及尿nephrin排泄量。雄性FVB/NJ秋田小鼠分别在4周龄和8周龄时出现持续性高血糖和蛋白尿。这些异常伴随着10周龄秋田小鼠的收缩压显著升高，这与心脏肥大的功能、结构和分子特征相关。到20周龄时，秋田小鼠的白蛋白尿、肾脏和肾小球肥大增加了10倍，足细胞数量减少。在30周龄的秋田小鼠中观察到轻度至中度肾小球系膜扩张。在4周龄的秋田小鼠中，高血糖症的发作伴随着足细胞凋亡的增加和尿中nephrin的排泄增加，然后出现蛋白尿。尿nephrin排泄也显着增加蛋白尿秋田小鼠在16和20周龄，并与白蛋白排泄率。这些数据表明：1. FVB/NJ秋田小鼠具有可用于研究糖尿病肾脏和心脏损伤机制的表型特征; FVB/NJ秋田小鼠尿nephrin排泄增加与肾损伤相关，并且在疾病过程的早期可检测到。
Akita mice are a genetic model of type 1 diabetes. In the present studies, we investigated the phenotype of Akita mice on the FVB/NJ background and examined urinary nephrin excretion as a marker of kidney injury. Male Akita mice were compared with non-diabetic controls for functional and structural characteristics of renal and cardiac disease. Podocyte number and apoptosis as well as urinary nephrin excretion were determined in both groups. Male FVB/NJ Akita mice developed sustained hyperglycemia and albuminuria by 4 and 8 weeks of age, respectively. These abnormalities were accompanied by a significant increase in systolic blood pressure in 10-week old Akita mice, which was associated with functional, structural and molecular characteristics of cardiac hypertrophy. By 20 weeks of age, Akita mice developed a 10-fold increase in albuminuria, renal and glomerular hypertrophy and a decrease in the number of podocytes. Mild-to-moderate glomerular mesangial expansion was observed in Akita mice at 30 weeks of age. In 4-week old Akita mice, the onset of hyperglycemia was accompanied by increased podocyte apoptosis and enhanced excretion of nephrin in urine before the development of albuminuria. Urinary nephrin excretion was also significantly increased in albuminuric Akita mice at 16 and 20 weeks of age and correlated with the albumin excretion rate. These data suggest that: 1. FVB/NJ Akita mice have phenotypic characteristics that may be useful for studying the mechanisms of kidney and cardiac injury in diabetes, and 2. Enhanced urinary nephrin excretion is associated with kidney injury in FVB/NJ Akita mice and is detectable early in the disease process.
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影响因子：
7.7
作者：
Pätäri, A;Forsblom, C;Holthöfer, H
通讯作者：
Holthöfer, H
影响因子：
2.2
作者：
Haseyama, T;Fujita, T;Koizumi, A
通讯作者：
Koizumi, A
影响因子：
19.6
作者：
LANE, PH;STEFFES, MW;MAUER, SM
通讯作者：
MAUER, SM
影响因子：
5.3
作者：
Donoviel, DB;Freed, DD;Powell, DR
通讯作者：
Powell, DR
影响因子：
13.6
作者：
Kim, Jin-Ju;Li, Jin Ji;Kang, Shin-Wook
通讯作者：
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