Faculty of Medical Sciences, Department of Clinical Biochemistry, Tarbiat Modares University, Tehran, Iran.
Biol Chem. 2013 Sep;394(9):1213-22. doi: 10.1515/hsz-2012-0355.
Differentiation of human mesenchymal stem cells (MSCs) to metabolically active hepatocytes depends on different regulatory factors. Trans-differentiation of stem cells into specific cell lineage in the presence of specific stimuli is associated with the molecular and cellular damage. The aim of the present study was to examine the role of P53 in the regulation of cyclooxygenase-2 (COX-2) expression and the generation of protein and lipid oxidation during trans-differentiation of MSCs into hepatocyte-like cells. During the 3-week differentiation process of MSCs to hepatocyte-like cells we found that expression liver-specific markers was associated with increased levels of lipid peroxidation and protein carbonyl formation. Expression of P53 and COX-2 at mRNA and protein levels were evaluated in MSCs before and after differentiation on days 7, 14 and 21. We showed that the up-regulation of COX-2 was associated with augmentation of the rate of cell proliferation, morphological and biochemical changes of hepatocytes-like cells. However, in parallel the P53 at the mRNA level was down-regulated, and at protein levels accumulation in the nuclei was reduced during the hepatogenic differentiation time. Our results may suggest a P53-COX-2 pathway in the regulation of hepatogenic differentiation of stem cells, which is linked to differentiation-dependent molecular oxidative damage.
人骨髓间充质干细胞（MSCs）向代谢活跃的肝细胞的分化取决于不同的调节因子。在特定刺激存在下，干细胞向特定细胞谱系的转分化与分子和细胞损伤有关。本研究的目的是研究 P53 在调节环氧化酶-2（COX-2）表达和 MSC 向肝样细胞分化过程中蛋白质和脂质氧化产生中的作用。在 MSC 向肝样细胞分化的 3 周过程中，我们发现肝特异性标志物的表达与脂质过氧化和蛋白质羰基形成水平的增加有关。在分化第 7、14 和 21 天，我们评估了 MSC 中 P53 和 COX-2 在 mRNA 和蛋白质水平上的表达。我们表明 COX-2 的上调与细胞增殖率的增加、肝样细胞的形态和生化变化有关。然而，与此同时，P53 在 mRNA 水平下调，而在蛋白水平上，核内的积累在肝发生分化时间内减少。我们的结果可能表明 P53-COX-2 途径在干细胞的肝发生分化调节中起作用，这与分化依赖性的分子氧化损伤有关。
