Department of Pharmacology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Lu, Haidian, Beijing, China.
Eur J Pharmacol. 2011 Mar 1;654(1):92-9. doi: 10.1016/j.ejphar.2010.12.008. Epub 2010 Dec 24.
Autosomal dominant polycystic kidney disease, a common inherited disease affecting about 1/1000 and 1/400 live births, is characterized by massive enlargement of fluid-filled cysts and eventually causes renal failure. The purpose of this study is to identify the inhibitory effect of curcumin on renal cyst development and to investigate the inhibitory mechanism. Madin-Darby canine kidney (MDCK) cyst model and murine embryonic kidney cyst model were used to evaluate inhibitory activity. Cell viability, proliferation, apoptosis, CFTR function and expression, and signaling pathways in MDCK cells were determined to explore the mechanism of cyst inhibition. Curcumin was found to significantly inhibit MDCK cyst development. At maximum dose curcumin caused 62% inhibition of the cyst formation (IC(50) was 0.12 μM). Curcumin slowed cyst enlargement in both MDCK cyst model and embryonic kidney cyst model with dose-response relationship. Curcumin neither induced cytotoxicity nor apoptosis in MDCK cells at <100 μM. Curcumin failed to affect the chloride transporter CFTR expression and function. Interestingly, curcumin inhibited forskolin-promoted cell proliferation and promoted the tubule formation in MDCK cells, which indicates curcumin promotes MDCK cell differentiation. Furthermore, curcumin reduced the intracellular signaling proteins Ras, B-raf, p-MEK, p-ERK, c-fos, Egr-1, but increased Raf-1 and NAB2 in MDCK cells exposed to forskolin. These results define that curcumin inhibits renal cyst formation and enlargement and suggest that curcumin might be developed as a candidate drug for polycystic kidney disease.
常染色体显性多囊肾病是一种常见的遗传性疾病，影响约每 1000 至 400 名活产儿中的 1 名，其特征是充满液体的囊肿大量增大，最终导致肾衰竭。本研究旨在确定姜黄素对肾囊肿发育的抑制作用，并探讨其抑制机制。使用犬肾传代细胞（MDCK）囊肿模型和鼠胚胎肾囊肿模型来评估抑制活性。测定 MDCK 细胞的细胞活力、增殖、凋亡、CFTR 功能和表达以及信号通路，以探讨抑制囊肿形成的机制。姜黄素显著抑制 MDCK 囊肿的发育。在最大剂量下，姜黄素引起的囊肿形成抑制率为 62%（IC50 为 0.12 μM）。姜黄素以剂量反应关系减缓了 MDCK 囊肿模型和胚胎肾囊肿模型中囊肿的扩大。在 <100 μM 时，姜黄素在 MDCK 细胞中既不引起细胞毒性也不引起细胞凋亡。姜黄素对氯离子转运体 CFTR 的表达和功能没有影响。有趣的是，姜黄素抑制了 forskolin 促进的 MDCK 细胞增殖，并促进了 MDCK 细胞的小管形成，这表明姜黄素促进了 MDCK 细胞的分化。此外，姜黄素降低了暴露于 forskolin的 MDCK 细胞中的细胞内信号蛋白 Ras、B-raf、p-MEK、p-ERK、c-fos、Egr-1，但增加了 Raf-1 和 NAB2。这些结果表明姜黄素抑制肾囊肿的形成和增大，并提示姜黄素可能被开发为多囊肾病的候选药物。
