Resveratrol protects podocytes against apoptosis via stimulation of autophagy in a mouse model of diabetic nephropathy

被引:92
作者
Huang, Shan-Shan [1 ,2 ]
Ding, Da-Fa [1 ]
Chen, Sheng [1 ]
Dong, Cheng-Long [3 ]
Ye, Xiao-Long [1 ]
Yuan, Yang-Gang [4 ]
Feng, Ya-Min [1 ]
You, Na [1 ]
Xu, Jia-Rong [1 ]
Miao, Heng [1 ]
You, Qiang [1 ]
Lu, Xiang [5 ]
Lu, Yi-Bing [1 ]
机构
[1] Nanjing Med Univ, Affiliated Hosp 2, Dept Endocrinol, Nanjing, Jiangsu, Peoples R China
[2] Nanjing Mil Command, Nanjing Gen Hosp, Dept Endocrinol, Nanjing, Jiangsu, Peoples R China
[3] Yancheng First Peoples Hosp, Dept Emergency, Yancheng, Peoples R China
[4] Nanjing Med Univ, Affiliated Hosp 1, Dept Nephrol, Nanjing, Jiangsu, Peoples R China
[5] Nanjing Med Univ, Affiliated Hosp 2, Dept Geriat, Nanjing, Jiangsu, Peoples R China
来源
SCIENTIFIC REPORTS | 2017年 / 7卷
基金
中国国家自然科学基金;
关键词
ENDOPLASMIC-RETICULUM STRESS; CELL; STREPTOZOTOCIN; PROTEINURIA; DYSFUNCTION; MECHANISM;
D O I
10.1038/srep45692
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Podocyte apoptosis coincides with albuminuria onset and precedes podocytopenia in diabetic nephropathy. However, there is a lack of effective therapeutic drugs to protect podocytes from apoptosis. Here, we demonstrated that resveratrol relieved a series of indicators of diabetic nephropathy and attenuated apoptosis of podocytes in db/db diabetic model mice. In addition, resveratrol induced autophagy in both db/db mice and human podocytes. Furthermore, inhibition of autophagy by 3-methyladenine (3-MA) and autophagy gene 5 (Atg5) short hairpin RNA (shRNA) reversed the protective effects of resveratrol on podocytes. Finally, we found that resveratrol might regulate autophagy and apoptosis in db/db mice and podocytes through the suppression of microRNA383-5p (miR-383-5p). Together, our results indicate that resveratrol effectively attenuates high glucoseinduced apoptosis via the activation of autophagy in db/db mice and podocytes, which involves miR383-5p. Thus, this study reveals a new possible strategy to treat diabetic nephropathy.
引用
收藏
页数:15
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