REDD1 Ablation Attenuates the Development of Renal Complications in Diabetic Mice.
REDD1 Ablation Attenuates the Development of Renal Complications in Diabetic Mice.
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作者：
慢性高血糖通过促进肾小球损伤促进糖尿病肾病的发展。在这项研究中，我们评估的假设，即高血糖条件下促进表达的应激反应蛋白调节的发展和DNA损伤反应1（REDD 1）在肾脏中的方式，有助于发展氧化应激和肾损伤。链脲佐菌素诱导糖尿病16周后，在野生型（WT）小鼠中观察到白蛋白尿和肾脏肥大，同时肾脏REDD1表达增加。相比之下，糖尿病REDD1敲除（KO）小鼠没有表现出肾生理功能受损。组织学检查显示，糖尿病REDD1 KO小鼠的肾小球损伤（包括系膜扩张、基质沉积和糖尿病WT小鼠肾脏中的足细胞减少）减少或不存在。在培养的人足细胞中，暴露于高血糖条件下增强了REDD1表达，增加了活性氧（ROS）水平，并促进了细胞死亡。在糖尿病小鼠的肾脏和暴露于高血糖条件下的足细胞培养物中，REDD1缺失减少了ROS并防止了足细胞损失。REDD1缺失的益处通过药理学GSK3β抑制得到了概括，支持REDD1依赖性GSK3β激活在糖尿病诱导的氧化应激和肾缺陷中的作用。结果支持REDD 1在糖尿病引起的肾脏并发症中的作用。
Chronic hyperglycemia contributes to development of diabetic kidney disease by promoting glomerular injury. In this study, we evaluated the hypothesis that hyperglycemic conditions promote expression of the stress response protein regulated in development and DNA damage response 1 (REDD1) in the kidney in a manner that contributes to the development of oxidative stress and renal injury. After 16 weeks of streptozotocin-induced diabetes, albuminuria and renal hypertrophy were observed in wild-type (WT) mice coincident with increased renal REDD1 expression. In contrast, diabetic REDD1 knockout (KO) mice did not exhibit impaired renal physiology. Histopathologic examination revealed that glomerular damage including mesangial expansion, matrix deposition, and podocytopenia in the kidneys of diabetic WT mice was reduced or absent in diabetic REDD1 KO mice. In cultured human podocytes, exposure to hyperglycemic conditions enhanced REDD1 expression, increased reactive oxygen species (ROS) levels, and promoted cell death. In both the kidney of diabetic mice and in podocyte cultures exposed to hyperglycemic conditions, REDD1 deletion reduced ROS and prevented podocyte loss. Benefits of REDD1 deletion were recapitulated by pharmacological GSK3β suppression, supporting a role for REDD1-dependent GSK3β activation in diabetes-induced oxidative stress and renal defects. The results support a role for REDD1 in diabetes-induced renal complications.
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影响因子：
7.7
作者：
通讯作者：
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DOI：
10.1152/ajprenal.00509.2020
发表时间：
2021-04-01
影响因子：
4.2
作者：
Lee, Hyun Soon;Suh, Ji Yeon;Lee, Eugene
通讯作者：
Lee, Eugene
影响因子：
19.6
作者：
Li, J. J.;Kwak, S. J.;Kang, S-W
通讯作者：
Kang, S-W
DOI：
10.1073/pnas.172398899
发表时间：
2002-09-03
影响因子：
11.1
作者：
Dinkova-Kostova, AT;Holtzclaw, WD;Talalay, P
通讯作者：
Talalay, P
影响因子：
64.5
作者：
KREIDBERG, JA;SARIOLA, H;JAENISCH, R
通讯作者：
JAENISCH, R