Naringenin Ameliorated Kidney Injury through Let-7a/TGFBR1 Signaling in Diabetic Nephropathy.
Naringenin Ameliorated Kidney Injury through Let-7a/TGFBR1 Signaling in Diabetic Nephropathy.
复制标题
柚皮素通过 Let-7a/TGFBR1 信号传导改善糖尿病肾病的肾损伤
DOI：
10.1155/2016/8738760
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发表时间：
2016
影响因子：
4.3
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Yan N;Wen L;Peng R;Li H;Liu H;Peng H;Sun Y;Wu T;Chen L;Duan Q;Sun Y;Zhou Q;Wei L;Zhang Z
糖尿病肾病是糖尿病最常见的并发症之一。然而，确切的机制尚不清楚。结果表明，NAR 50 mg/d治疗6周后，DN大鼠24 h尿蛋白定量、肾指数、肾小球面积均下降，肌酐清除率升高。NAR组肾小球系膜细胞（MMCs）增殖受3，（4，5-二甲基-2-噻唑基）-2，5-二苯基-2H-溴化四氮唑（MTT）抑制，细胞周期分析显示细胞停留在G2期。NAR治疗可减轻DN大鼠及MMCs的ECM沉积。此外，我们的数据表明，let-7a在糖尿病肾病大鼠和MMCs在高糖条件下表达下调。NAR可通过上调let-7a影响MMCs中Col 4和FN的表达。此外，我们还发现let-7a负性调节转化生长因子β1受体1（TGF-β1 receptor 1，TGFBR 1）的表达，而TGF-β1/smad信号通路的下调需要TGF-β1受体1的参与。有趣的是，NAR通过上调let-7a来抑制TGF-β1/smads信号通路的激活。因此，我们的研究结果表明，NAR通过调节let-7a/TGFBR 1信号转导来改善肾损伤。
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-β1 receptor 1 (TGFBR1), and TGFBR1 was required for the let-7a-mediated downregulation of TGF-β1/smad signaling. Interestingly, NAR inhibited TGF-β1/smads signaling activation by upregulating let-7a. Therefore, our findings indicated that NAR ameliorated kidney injury by regulating let-7a/TGFBR1 signaling.