The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu 210029, China.
Evid Based Complement Alternat Med. 2015;2015:619720. doi: 10.1155/2015/619720. Epub 2015 Apr 8.
Renal fibrosis is a common cause of renal dysfunction with chronic kidney disease. Central to this process is epithelial-mesenchymal transformation (EMT) of proximal tubular epithelial cells driven by transforming growth factor-β1 (TGF-β1) signaling. The present study aimed to investigate the effect of Ferulic acid (FA) on EMT of renal proximal tubular epithelial cell line (NRK-52E) induced by TGF-β1 and to elucidate its underlying mechanism against EMT related to TGF-β1/Smads pathway. The NRK-52E cells were treated for 48 h with TGF-β1 (5 ng/mL) in different concentrations of FA (0 to 200 µM). Fibronectin, a mesenchymal marker, was assessed by western blotting. Western blotting was also used to examine the EMT markers (E-cadherin, and α-smooth muscle actin (α-SMA)), signal transducer (p-Smad2/3), and EMT initiator (Snail). ILK was also assayed by western blotting. The results showed that TGF-β1 induced spindle-like morphological transition in NRK-52E cells. Smad2/3 signaling pathway activation, increased fibronectin, α-SMA, ILK, and Snail expression, and decreased E-cadherin expression in TGF-β1-treated NRK-52E cells. FA efficiently blocked P-Smad2/3 activation and attenuated all these EMT changes induced by TGF-β1. These findings suggest that FA may serve as a potential fibrosis antagonist for renal proximal tubule cells by inhibiting EMT process.
肾纤维化是慢性肾脏病导致肾功能障碍的常见原因。这个过程的核心是转化生长因子-β1（TGF-β1）信号驱动的近端肾小管上皮细胞的上皮-间充质转化（EMT）。本研究旨在探讨阿魏酸（FA）对 TGF-β1诱导的肾近端肾小管上皮细胞系（NRK-52E）EMT 的影响，并阐明其对 TGF-β1/Smads 通路相关 EMT 的潜在机制。将 NRK-52E 细胞用不同浓度的 FA（0 至 200μM）处理 48 小时，用 TGF-β1（5ng/ml）处理。通过 Western blot 检测间充质标志物纤维连接蛋白。Western blot 还用于检测 EMT 标志物（E-钙黏蛋白和α-平滑肌肌动蛋白（α-SMA））、信号转导（p-Smad2/3）和 EMT 启动子（Snail）。还通过 Western blot 检测 ILK。结果表明，TGF-β1 诱导 NRK-52E 细胞发生梭形形态转变。Smad2/3 信号通路激活，增加纤维连接蛋白、α-SMA、ILK 和 Snail 的表达，降低 TGF-β1 处理的 NRK-52E 细胞中 E-钙黏蛋白的表达。FA 能有效阻断 P-Smad2/3 激活，并减弱 TGF-β1 诱导的所有这些 EMT 变化。这些发现表明，FA 可能通过抑制 EMT 过程，成为肾近端小管细胞潜在的抗纤维化拮抗剂。
