Impaired Albumin Uptake and Processing Promote Albuminuria in OVE26 Diabetic Mice.
Impaired Albumin Uptake and Processing Promote Albuminuria in OVE26 Diabetic Mice.
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DOI：
10.1155/2016/8749417
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发表时间：
2016
影响因子：
4.3
通讯作者：
Epstein PN
中科院分区：
文献类型：
--
作者：
Long YS;Zheng S;Kralik PM;Benz FW;Epstein PN
近端小管功能障碍对糖尿病蛋白尿的重要性尚不确定。在所有糖尿病小鼠模型中，OVE26小鼠有最严重的蛋白尿，但尚不清楚肾小管摄取和处理受损是否是促成因素。在目前的研究中，荧光白蛋白被用来跟踪白蛋白在OVE26和正常小鼠中的命运。与正常尿液相比，OVE26尿液中完整荧光白蛋白的含量至少增加了23倍，而70 KD的荧光葡聚糖的含量仅增加了3倍。这表明，OVE26蛋白尿与肾小球大小选择性筛选不同。正常肾小管和糖尿病肾小管注射后3 小时的白蛋白显像结果相似。然而，注射3天后，OVE26小管的一部分仍保持着强烈的白蛋白荧光，这在正常小鼠中从未观察到。注射白蛋白滞留时间长的肾小管丧失摄取白蛋白的能力，不能排出荧光白蛋白的肾小管与总蛋白尿有显着相关性。TUNEL染色显示，保留荧光白蛋白的OVE26小管的细胞死亡增加了76倍。这些结果表明，不能处理和处理内化白蛋白会导致白蛋白摄取受损、蛋白尿增加和肾小管细胞凋亡。
The importance of proximal tubules dysfunction to diabetic albuminuria is uncertain. OVE26 mice have the most severe albuminuria of all diabetic mouse models but it is not known if impaired tubule uptake and processing are contributing factors. In the current study fluorescent albumin was used to follow the fate of albumin in OVE26 and normal mice. Compared to normal urine, OVE26 urine contained at least 23 times more intact fluorescent albumin but only 3-fold more 70 kD fluorescent dextran. This indicated that a function other than size selective glomerular sieving contributed to OVE26 albuminuria. Imaging of albumin was similar in normal and diabetic tubules for 3 hrs after injection. However 3 days after injection a subset of OVE26 tubules retained strong albumin fluorescence, which was never observed in normal mice. OVE26 tubules with prolonged retention of injected albumin lost the capacity to take up albumin and there was a significant correlation between tubules unable to eliminate fluorescent albumin and total albuminuria. TUNEL staining revealed a 76-fold increase in cell death in OVE26 tubules that retained fluorescent albumin. These results indicate that failure to process and dispose of internalized albumin leads to impaired albumin uptake, increased albuminuria, and tubule cell apoptosis.
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影响因子：
19.6
作者：
Motoyoshi, Yaeko;Matsusaka, Taiji;Saito, Akihiko;Pastan, Ira;Willnow, Thomas E.;Mizutani, Shuki;Ichikawa, Iekuni
通讯作者：
Ichikawa, Iekuni
DOI：
10.1002/ar.a.10038
发表时间：
2003-04-01
期刊：
ANATOMICAL RECORD PART A-DISCOVERIES IN MOLECULAR CELLULAR AND EVOLUTIONARY BIOLOGY
影响因子：
--
作者：
Carlson, EC;Audette, JL;Epstein, PN
通讯作者：
Epstein, PN
影响因子：
8
作者：
Carlson, Edward C.;Chhoun, Jennifer M.;Epstein, Paul N.
通讯作者：
Epstein, Paul N.
影响因子：
7.7
作者：
Osicka, TM;Houlihan, CA;Comper, WD
通讯作者：
Comper, WD
影响因子：
9.2
作者：
Xu J;Zheng S;Kralik PM;Krishnan L;Huang H;Hoying JB;Cai L;Carlson EC;Tan Y;Epstein PN
通讯作者：
Epstein PN