Department of Nephrology, Second Affiliated Hospital, Zhe Jiang University School of Medicine, Hangzhou, People's Republic of China.
Am J Nephrol. 2010;31(4):332-41. doi: 10.1159/000287230. Epub 2010 Feb 17.
Curcumin, a polyphenolic compound derived from rhizomes of Curcuma spp., has been shown to possess potent anti-fibrotic properties. Here, we investigate the role of curcumin in modulating the profibrotic action of TGF-beta in human proximal tubule cells (HK-2) and its underlying mechanisms.
HK-2 cells were stimulated with 5 ng/ml TGF-beta(1). The effects of curcumin on TGF-beta(1)-regulated gene expression and Smad phosphorylation were analyzed by RT-PCR, ELISA and Western blotting.
Curcumin inhibited TGF-beta(1)-induced plasminogen activator inhibitor-1 (PAI-1), alpha-smooth muscle actin (alpha-SMA) mRNA and protein expression. Curcumin suppressed not only TGF-beta(1)-induced Smad2 phosphorylation in a dose- and time-dependent manner, but also the nuclear accumulation of receptor-regulated Smads (R-Smad), Smad2 and Smad3. A serine/threonine protein phosphatase inhibitor (microcystin) could partly reverse the inhibitory effect of curcumin on Smad phosphorylation.
Curcumin blocks the profibrotic actions of TGF-beta on HK-2 cells through the down-regulation of the Smad signaling pathway, and curcumin may have some similar effect as serine/threonine protein phosphatases. Our findings suggest curcumin as a potential candidate for treatment of tubulointerstitial fibrosis.
姜黄素是一种从姜黄属植物根茎中提取的多酚化合物，已被证明具有很强的抗纤维化特性。在这里，我们研究了姜黄素在调节人近端肾小管细胞（HK-2）中 TGF-β的促纤维化作用及其潜在机制中的作用。
用 5ng/mlTGF-β(1)刺激 HK-2 细胞。通过 RT-PCR、ELISA 和 Western blot 分析姜黄素对 TGF-β(1)调节的基因表达和 Smad 磷酸化的影响。
姜黄素抑制 TGF-β(1)诱导的纤溶酶原激活物抑制剂-1（PAI-1）、α-平滑肌肌动蛋白（α-SMA）mRNA 和蛋白表达。姜黄素不仅以剂量和时间依赖的方式抑制 TGF-β(1)诱导的 Smad2 磷酸化，而且还抑制受体调节的 Smads（R-Smad）、Smad2 和 Smad3 的核积累。丝氨酸/苏氨酸蛋白磷酸酶抑制剂（微囊藻素）可部分逆转姜黄素对 Smad 磷酸化的抑制作用。
姜黄素通过下调 Smad 信号通路阻断 TGF-β对 HK-2 细胞的促纤维化作用，姜黄素可能具有与丝氨酸/苏氨酸蛋白磷酸酶相似的作用。我们的发现表明姜黄素可能是治疗肾小管间质纤维化的潜在候选药物。
