Apoptosis induced by endoplasmic reticulum stress involved in diabetic kidney disease
Apoptosis induced by endoplasmic reticulum stress involved in diabetic kidney disease
复制标题
DOI：
10.1016/j.bbrc.2008.04.031
复制
发表时间：
2008-06-13
影响因子：
3.1
通讯作者：
Ge, Zhiming
中科院分区：
文献类型：
--
作者：
Liu, Guanghui;Sun, Yingying;Ge, Zhiming
内质网应激已被认为在糖尿病并发症的发病机制中起着至关重要的作用。但其是否参与了糖尿病肾病的肾损伤尚不清楚。我们研究了ER相关凋亡在链脲佐菌素（STZ）诱导的糖尿病大鼠肾脏疾病中的参与。通过尿蛋白检测、苏木精-伊红（H&E）染色和TUNEL法检测糖尿病肾病的存在和细胞凋亡的增强。我们采用免疫组化、Western印迹和实时荧光PCR分析ER分子伴侣和ER相关凋亡的指标。与对照组相比，ER伴侣GRP 78在糖尿病肾脏中显著上调。此外，ER相关凋亡的三个标志，C/EBP同源蛋白（CHOP），c-JUN NH 2-末端激酶（JNK）和caspase-12，被发现在糖尿病肾脏中被激活。这些结果提示糖尿病肾病的发生可能与内质网应激诱导的细胞凋亡有关。(c)2008年爱思唯尔公司All rights reserved.
Endoplasmic reticulum stress has been suggested to play a crucial role in the pathogenesis of diabetic complications. However, whether it is involved in the renal injury of diabetic nephropathy is still not known. We investigated the involvement of ER-associated apoptosis in kidney disease of streptozocin (STZ)-induced diabetic rats. We used albuminuria examination, hematoxylin & eosin (H&E) staining and TUNEL analysis to identify the existence of diabetic nephropathy and enhanced apoptosis. We performed immunohistochemistry, Western blot, and real-time PCR to analyze indicators of ER molecule chaperone and ER-associated apoptosis. GRP78, the ER chaperone, was up-regulated significantly in diabetic kidney compared to control. Furthermore, three hallmarks of ER-associated apoptosis, C/EBP homologous protein (CHOP), c-JUN NH2-terminal kinase (JNK) and caspase-12, were found to have activated in the diabetic kidney. Taken together, those results suggested that apoptosis induced by ER stress occurred in diabetic kidney, which may contribute to the development of diabetic nephropathy. (c) 2008 Elsevier Inc. All rights reserved.