Li Xuejuan, Liu Weihua, Wang Qin, Liu Peiqing, Deng Yanhui, Lan Tian, Zhang Xiaoyan, Qiu Baoming, Ning Hairong, Huang Heqing
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guagnzhou, Guangdong, China.
Mol Cell Endocrinol. 2009 Aug 13;307(1-2):157-62. doi: 10.1016/j.mce.2009.03.006. Epub 2009 Mar 24.
Our previous findings demonstrated that emodin could improve the renal function in rats with diabetic nephropathy, but little is known about its molecular mechanisms. In this study, we investigated the effects of emodin on high glucose (HG)-induced cell proliferation and fibronectin (FN) protein expression in rat mesangial cells, and explored the possible mechanism. Cell proliferation and cell cycle were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assay, respectively. The protein levels of FN, p-p38MAPK, t-p38MAPK, p-CREB, PPARgamma, and CTGF in rat mesangial cells were detected by Western blot. Our results demonstrated that emodin significantly suppressed HG-induced cell proliferation and arrested cell cycle progress. Protein expression of FN, phospho-p38MAPK, phospho-CREB and CTGF was markedly reduced, and PPARgamma protein level was significantly increased after emodin treatment. In conclusion, emodin suppressed HG-induced cell proliferation and FN expression in rat mesangial cells through inhibiting the p38MAPK pathway involved CREB, PPAPgamma and CTGF, suggesting a potential role of emodin in the treatment of diabetic nephropathy.
我们之前的研究结果表明，大黄素可改善糖尿病肾病大鼠的肾功能，但其分子机制尚不清楚。在本研究中，我们研究了大黄素对高糖（HG）诱导的大鼠系膜细胞增殖和纤连蛋白（FN）蛋白表达的影响，并探讨了其可能的机制。分别采用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐（MTT）法和流式细胞术检测细胞增殖和细胞周期。通过蛋白质免疫印迹法检测大鼠系膜细胞中FN、磷酸化p38丝裂原活化蛋白激酶（p-p38MAPK）、总p38丝裂原活化蛋白激酶（t-p38MAPK）、磷酸化环磷腺苷反应元件结合蛋白（p-CREB）、过氧化物酶体增殖物激活受体γ（PPARγ）和结缔组织生长因子（CTGF）的蛋白水平。我们的结果表明，大黄素显著抑制HG诱导的细胞增殖并阻滞细胞周期进程。大黄素处理后，FN、磷酸化p38MAPK、磷酸化CREB和CTGF的蛋白表达明显降低，而PPARγ蛋白水平显著升高。总之，大黄素通过抑制涉及CREB、PPARγ和CTGF的p38MAPK途径，抑制HG诱导的大鼠系膜细胞增殖和FN表达，提示大黄素在糖尿病肾病治疗中具有潜在作用。
