Sun Li-na, Chen Zhi-xin, Liu Xiang-chun, Liu Hai-ying, Guan Guang-ju, Liu Gang
Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong, China.
Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong, China.
Biomed Pharmacother. 2014 Oct;68(8):1079-88. doi: 10.1016/j.biopha.2014.10.005. Epub 2014 Oct 25.
Epithelial-mesenchymal transition (EMT) is recognized to play a key role in diabetic nephropathy (DN). Curcumin, the main active component of turmeric extracted from the roots of the Curcuma longa plant, has been reported for its anti-fibrotic effects in kidney fibrosis. The purpose of our study was to investigate the effects of curcumin in reversing epithelial-to-mesenchymal transition (EMT) of podocytes in vivo and in vitro.
MATERIALS/METHODS: In vivo streptozotocin (STZ)-induced diabetic rats received vehicle or curcumin, and podocytes were treated with high glucose (HG) in the presence or absence of curcumin in vitro. And we investigated the effect of curcumin on HG-induced phosphorylation of cav-1 on the stability cav-1 and β-catenin using immunoprecipitation and fluorescence microscopy analysis.
Curcumin treatment dramatically ameliorated metabolic parameters, renal function, morphological parameters in diabetic rats. We found that HG treatment led to significant down-regulation of p-cadherin and synaptopodin, as well as remarkable up-regulation of α-SMA and FSP-1 in vivo and in vitro. Furthermore, curcumin inhibited HG-induced caveolin-1 (cav-1) Tyr(14) phosphorylation associating with the suppression of stabilization of cav-1 and β-catenin.
In summary, these findings suggest that curcumin prevents EMT of podocytes, proteinuria, and kidney injury in DN by suppressing the phosphorylation of cav-1, and increasing stabilization of cav-1 and β-catenin.
上皮-间质转化（EMT）被认为在糖尿病肾病（DN）中起关键作用。姜黄素是从姜黄属植物姜黄根中提取的姜黄的主要活性成分，已有报道称其在肾纤维化中具有抗纤维化作用。我们研究的目的是调查姜黄素在体内和体外逆转足细胞上皮-间质转化（EMT）的作用。
材料/方法：体内实验中，链脲佐菌素（STZ）诱导的糖尿病大鼠接受溶剂或姜黄素处理，体外实验中，足细胞在有或无姜黄素存在的情况下用高糖（HG）处理。我们使用免疫沉淀和荧光显微镜分析研究了姜黄素对HG诱导的小窝蛋白-1（cav-1）磷酸化、cav-1稳定性和β-连环蛋白的影响。
姜黄素治疗显著改善了糖尿病大鼠的代谢参数、肾功能和形态学参数。我们发现，HG处理导致体内和体外p-钙黏蛋白和突触素显著下调，以及α-平滑肌肌动蛋白（α-SMA）和波形蛋白1（FSP-1）显著上调。此外，姜黄素抑制HG诱导的小窝蛋白-1（cav-1）酪氨酸（Tyr14）磷酸化，同时抑制cav-1和β-连环蛋白的稳定性。
总之，这些发现表明姜黄素通过抑制cav-1磷酸化以及增加cav-1和β-连环蛋白的稳定性，预防DN中足细胞的EMT、蛋白尿和肾损伤。
