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齐墩果酸可减轻 TGF-β1 诱导的 NRK-52E 细胞上皮间质转化。

Oleanolic acid attenuates TGF-β1-induced epithelial-mesenchymal transition in NRK-52E cells.

机构信息

Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, Jiangsu, China.

The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.

出版信息

BMC Complement Altern Med. 2018 Jul 4;18(1):205. doi: 10.1186/s12906-018-2265-y.

DOI:10.1186/s12906-018-2265-y
PMID:29973206
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6031099/
Abstract

BACKGROUND

Epithelial-to-mesenchymal transition (EMT) plays an important role in the progression of renal interstitial fibrosis, which finally leads to renal failure. Oleanolic acid (OA), an activator of NF-E2-related factor 2 (Nrf2), is reported to attenuate renal fibrosis in mice with unilateral ureteral obstruction. However, the role of OA in the regulation of EMT and the underlying mechanisms remain to be investigated. This study aimed to evaluate the effects of OA on EMT of renal proximal tubular epithelial cell line (NRK-52E) induced by TGF-β1, and to elucidate its underlying mechanism.

METHODS

Cells were incubated with TGF-β1 in the presence or absence of OA. The epithelial marker E-cadherin, the mesenchymal markers, α-smooth muscle actin (α-SMA), fibronectin, Nrf2, klotho, the signal transducer (p-Smad2/3), EMT initiator (Snail), and ILK were assayed by western blotting.

RESULTS

Our results showed that the NRK-52E cells incubated with TGF-β1 induced EMT with transition to the spindle-like morphology, down-regulated the expression of E-cadherin but up-regulated the expression of α-SMA and fibronectin. However, the treatment with OA reversed all EMT markers in a dose-dependent manner. OA also restored the expression of Nrf2 and klotho, decreased the phosphorylation of Smad2/3, ILK, and Snail in cells which was initiated by TGF-β1.

CONCLUSION

OA can attenuate TGF-β1 mediate EMT in renal tubular epithelial cells and may be a promising therapeutic agent in the treatment of renal fibrosis.

摘要

背景

上皮间质转化（EMT）在肾间质纤维化的进展中起着重要作用，最终导致肾衰竭。齐墩果酸（OA）是核因子 E2 相关因子 2（Nrf2）的激活剂，据报道可减轻单侧输尿管梗阻小鼠的肾纤维化。然而，OA 在调节 EMT 中的作用及其潜在机制仍有待研究。本研究旨在评估 OA 对 TGF-β1 诱导的肾近端肾小管上皮细胞系（NRK-52E）EMT 的影响，并阐明其潜在机制。

方法

用 TGF-β1 孵育细胞，或在 OA 存在或不存在的情况下孵育细胞。上皮标志物 E-钙黏蛋白、间充质标志物α-平滑肌肌动蛋白（α-SMA）、纤连蛋白、Nrf2、klotho、信号转导物（p-Smad2/3）、EMT 启动子（Snail）和 ILK 通过 Western 印迹法进行检测。

结果

我们的结果表明，用 TGF-β1 孵育的 NRK-52E 细胞诱导 EMT，向纺锤形形态转变，E-钙黏蛋白表达下调，α-SMA 和纤连蛋白表达上调。然而，OA 以剂量依赖性方式逆转所有 EMT 标志物。OA 还恢复了 Nrf2 和 klotho 的表达，降低了 TGF-β1 诱导的 Smad2/3、ILK 和 Snail 磷酸化。

结论

OA 可减轻 TGF-β1 介导的肾小管上皮细胞 EMT，可能是治疗肾纤维化的有前途的治疗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf2/6031099/bb7457303543/12906_2018_2265_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf2/6031099/cef96eff5c8b/12906_2018_2265_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf2/6031099/eb3a2d3afc99/12906_2018_2265_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf2/6031099/042052d11e99/12906_2018_2265_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf2/6031099/0d7848e9c6ea/12906_2018_2265_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf2/6031099/c9a6e68496e5/12906_2018_2265_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf2/6031099/bb7457303543/12906_2018_2265_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf2/6031099/cef96eff5c8b/12906_2018_2265_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf2/6031099/eb3a2d3afc99/12906_2018_2265_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf2/6031099/042052d11e99/12906_2018_2265_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf2/6031099/0d7848e9c6ea/12906_2018_2265_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf2/6031099/c9a6e68496e5/12906_2018_2265_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddf2/6031099/bb7457303543/12906_2018_2265_Fig6_HTML.jpg

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