Curcumin protects renal tubular epithelial cells from high glucose-induced epithelial-to-mesenchymal transition through Nrf2-mediated upregulation of heme oxygenase-1.
Curcumin protects renal tubular epithelial cells from high glucose-induced epithelial-to-mesenchymal transition through Nrf2-mediated upregulation of heme oxygenase-1.
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姜黄素通过 Nrf2 介导的血红素氧合酶 1 上调来保护肾小管上皮细胞免受高葡萄糖诱导的上皮间质转化。
DOI：
10.3892/mmr.2015.3556
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发表时间：
2015-07
影响因子：
3.4
通讯作者：
Chi Zhi-Hong
中科院分区：
文献类型：
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作者：
Li Hongjuan;Zhao Yue;Lu Shumin;Chi Zhi-Hong
已观察到姜黄素在肝、肺和胆囊中表现出抗纤维化作用。然而，姜黄素的细胞保护作用的机制仍有待阐明。肾脏中成熟肾小管上皮细胞的上皮-间质转化（EMT）被认为有助于与糖尿病肾病相关的基质蛋白在肾脏中的积聚。EMT还与肾间质纤维化和氧化应激的进展密切相关。这一过程可能通过肾小管上皮细胞中核因子（红细胞衍生2）样2（Nrf 2）和血红素加氧酶-1（HO-1）的激活消除高糖（HG）诱导的氧化应激而发生。在本研究中，姜黄素对HG诱导的NRK-52 E正常大鼠肾小管上皮细胞系EMT的影响进行了研究，并检查姜黄素的作用是否是通过诱导Nrf 2和HO-1表达介导的。目前的研究表明，姜黄素能够预防EMT相关事件，包括下调E-cadherin和增加α-平滑肌肌动蛋白的表达。进一步的分析显示，与对照组相比，姜黄素预处理的NRK-52 E细胞中Nrf 2和HO-1蛋白的表达水平在更大程度上升高。值得注意的是，用小干扰RNA敲低Nrf 2阻止了姜黄素诱导的HO-1表达升高和相关的抗纤维化作用。总之，本研究结果表明，姜黄素可能是重要的细胞抗氧化防御，通过激活Nrf 2和HO-1，从而保护NRK-52 E细胞从HG诱导的EMT。
Curcumin has been observed to exhibit an anti-fibrotic effect in the liver, lung and gallbladder. However, the mechanisms underlying the cytoprotective effects of curcumin remain to be elucidated. The epithelial-to-mesenchymal transition (EMT) of mature tubular epithelial cells in the kidney is considered to contribute to the renal accumulation of matrix proteins associated with diabetic nephropathy. The EMT is also closely associated with the progression of renal interstitial fibrosis and oxidative stress. This process may occur through abrogation of high glucose (HG)-induced oxidative stress via activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 (HO-1) in kidney tubular epithelial cells. In the present study, the effect of curcumin on HG-induced EMT in the NRK-52E normal rat kidney tubular epithelial cell line was investigated, and whether the effect of curcumin was mediated by the induction of Nrf2 and HO-1 expression was examined. The present study revealed that curcumin was able to prevent events associated with EMT, including the downregulation of E-cadherin and the increased expression of α-smooth muscle actin. Further analysis revealed that the expression levels of Nrf2 and HO-1 protein were elevated to a greater extent in the curcumin pretreated NRK-52E cells compared with those of the control. Notably, knockdown of Nrf2 with small interfering RNA prevented the curcumin-induced elevation in expression of HO-1 and the associated anti-fibrotic effects. In conclusion, the present findings suggested that curcumin may be significant in cellular antioxidant defense, through the activation of Nrf2 and HO-1, thereby protecting the NRK-52E cells from HG-induced EMT.
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影响因子：
--
作者：
Simonian, Michael H;Smith, John A
通讯作者：
Smith, John A
姜黄素上调转录因子 Nrf2、HO-1 表达并保护大鼠大脑免受局灶性缺血
影响因子：
2.9
作者：
Yang, Chenhui;Zhang, Xiangjian;Liu, Ying
通讯作者：
Liu, Ying
DOI：
10.1152/ajprenal.90500.2008
发表时间：
2009-03-01
影响因子：
4.2
作者：
Hills, Claire E.;Al-Rasheed, Nawal;Brunskill, Nigel J.
通讯作者：
Brunskill, Nigel J.
DOI：
10.1111/j.1742-7843.2007.00109.x
发表时间：
2007-10-01
影响因子：
3.1
作者：
Murugan, Pidaran;Pari, Leelavinothan
通讯作者：
Pari, Leelavinothan
影响因子：
7.7
作者：
Jiang T;Huang Z;Lin Y;Zhang Z;Fang D;Zhang DD
通讯作者：
Zhang DD