Naringenin Ameliorated Kidney Injury through Let-7a/TGFBR1 Signaling in Diabetic Nephropathy

被引:61
作者
Yan, Ning [1 ]
Wen, Li [1 ,2 ]
Peng, Rui [3 ]
Li, Hongmei [4 ]
Liu, Handeng [1 ]
Peng, Huimin [1 ]
Sun, Yan [1 ]
Wu, Tianhui [1 ]
Chen, Lei [5 ]
Duan, Qingrui [5 ]
Sun, Yixuan [5 ]
Zhou, Qin [5 ]
Wei, Lijiang [6 ]
Zhang, Zheng [1 ,2 ]
机构
[1] Chongqing Med Univ, Mol Med & Canc Res Ctr, Chongqing 400016, Peoples R China
[2] Chongqing Med Univ, Dept Cell Biol & Genet, Chongqing 400016, Peoples R China
[3] Chongqing Med Univ, Dept Bioinformat, Chongqing 400016, Peoples R China
[4] Chongqing Red Cross Hosp, Chongqing 400016, Peoples R China
[5] Chongqing Med Univ, Clin Coll 2, Chongqing 400016, Peoples R China
[6] Chongqing Med Univ, Clin Coll 1, Chongqing 400016, Peoples R China
关键词
EXTRACELLULAR-MATRIX; CELL-PROLIFERATION; OXIDATIVE STRESS; DOWN-REGULATION; EXPRESSION; INFLAMMATION; RAT; HYPERGLYCEMIA; INVASION; COLLAGEN;
D O I
10.1155/2016/8738760
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus (DM). However, the exact mechanism is not clearly understood. In this study, our results showed that 24 h urinary protein, kidney index, and glomerular area were decreased, while creatinine clearance ratio was increased in DN rats when the rats were treated with NAR 50 mg/d for 6 weeks. Mesangial cell (MMCs) proliferation was inhibited in the NAR group by 3,(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), and the cell cycle analysis showed that cells stayed in G2 phase in NAR group. And NAR treatment attenuated the deposition of ECM in DN rats and MMCs. Moreover, our data showed that let-7a was downexpressed in both DN rats and MMCs under high glucose condition. Surprisingly, NAR affected the expressions of Col4 and FN through upregulating let-7a in MMCs. In addition, we found that let-7a negatively regulated the expression of transforming growth factor-beta 1 receptor 1 (TGFBR1), and TGFBR1 was required for the let-7a-mediated downregulation of TGF-beta 1/smad signaling. Interestingly, NAR inhibited TGF-beta/smads signaling activation by upregulating let-7a. Therefore, our findings indicated that NAR ameliorated kidney injury by regulating let-7a/TGFBR1 signaling.
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页数:13
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