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Ursodeoxycholic acid and 4-phenylbutyrate prevent endoplasmic reticulum stress-induced podocyte apoptosis in diabetic nephropathy 期刊论文

编号：

5c5c5a28-d31d-43fc-a859-ee57d86eafe4
作者：

Cao, AiLi(曹爱丽)#^[1]Wang, Li(王利)#^[1]Chen, Xia^[2];Wang, YunMan^[2];Guo, HengJiang^[1];Chu, Shuang^[1];Liu, Cheng^[1];Zhang, XueMei*^[3]Peng, Wen(彭文)*^[2]
语种：

英文
期刊：

LABORATORY INVESTIGATION ISSN：0023-6837 2016 年 96 卷 6 期 (610 - 622) ; JUN
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摘要：

Endoplasmic reticulum (ER) stress, resulting from the accumulation of misfolded and/or unfolded proteins in ER membranes, is involved in the pathogenesis of diabetic nephropathy (DN). The aim of this study was to investigate the role of ER stress inhibitors ursodeoxycholic acid (UDCA) and 4-phenylbutyrate (4-PBA) in the treatment of DN in db/db mice. Findings have revealed that diabetic db/db mice were more hyperglycemic than their non-diabetic controls, and exhibited a marked increase in body weight, water intake, urine volume, fasting plasma glucose, systolic blood pressure, glucose and insulin tolerance. UDCA (40 mg/kg/day) or 4-PBA (100 mg/kg/day) treatment for 12 weeks resulted in an improvement in these biochemical and physical parameters. Moreover, UDCA or 4-PBA intervention markedly decreased urinary albuminuria and attenuated mesangial expansion in diabetic db/db mice, compared with db/db mice treated with vehicle. These beneficial effects of UDCA or 4-PBA on DN were associated with the inhibition of ER stress, as evidenced by the decreased expression of BiP, phospho-IRE1 alpha, phospho-eIF2 alpha, CHOP, ATF-6 and spliced X-box binding protein-1 in vitro and in vivo. UDCA or 4-PBA prevented hyperglycemia-induced or high glucose (HG)-induced apoptosis in podocytes in vivo and in vitro via the inhibition of caspase-3 and caspase-12 activation. Autophagy deficiency was also seen in glomeruli in diabetic mice and HG-incubated podocytes, exhibiting decreased expression of LC3B and Beclin-1, which could be restored by UDCA or 4-PBA treatment. Taken together, our results have revealed an important role of ER stress in the development of DN, and UDCA or 4-PBA treatment may be a potential novel therapeutic approach for the treatment of DN.
推荐引用方式
GB/T 7714：

Cao Ai-Li,Wang Li,Chen Xia, et al. Ursodeoxycholic acid and 4-phenylbutyrate prevent endoplasmic reticulum stress-induced podocyte apoptosis in diabetic nephropathy [J].LABORATORY INVESTIGATION,2016,96(6):610-622.
APA：

Cao Ai-Li,Wang Li,Chen Xia,Wang Yun-Man,&Peng Wen.(2016).Ursodeoxycholic acid and 4-phenylbutyrate prevent endoplasmic reticulum stress-induced podocyte apoptosis in diabetic nephropathy .LABORATORY INVESTIGATION,96(6):610-622.
MLA：

Cao Ai-Li, et al. "Ursodeoxycholic acid and 4-phenylbutyrate prevent endoplasmic reticulum stress-induced podocyte apoptosis in diabetic nephropathy" .LABORATORY INVESTIGATION 96,6(2016):610-622.
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