In Vitro and In Vivo Effects of Metformin on Osteopontin Expression in Mice Adipose-Derived Multipotent Stromal Cells and Adipose Tissue.

In Vitro and In Vivo Effects of Metformin on Osteopontin Expression in Mice Adipose-Derived Multipotent Stromal Cells and Adipose Tissue.
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二甲双胍对小鼠脂肪衍生的多能基质细胞和脂肪组织中骨桥蛋白表达的体外和体内作用。

DOI:
10.1155/2015/814896
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发表时间:
2015
影响因子:
4.3
通讯作者:
Marycz K
Marycz K
中科院分区:
医学3区
文献类型:
--
作者:
Śmieszek A;Basińska K;Chrząstek K;Marycz K

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二甲双胍不仅用作抗糖尿病药物,还用于治疗肥胖症或作为抗衰老药物。研究的第一部分讨论了浓度为 1 mM、5 mM 和 10 mM 的二甲双胍对体外小鼠脂肪源性多能间充质基质细胞 (ASC) 的形态、超微结构和增殖潜力的影响。此外,我们还确定了二甲双胍对小鼠脂肪组织代谢的影响。这项研究首次表明二甲双胍在体外以剂量和时间依赖性方式抑制 ASC 的增殖潜力。此外,我们还发现ASCs和骨桥蛋白的活性在mRNA和蛋白质水平上存在显着相关性。此外,我们还证明5mM和10mM二甲双胍对ASC具有细胞毒性作用,引起严重的形态、超微结构和凋亡变化。二甲双胍治疗动物脂肪组织中 OPN 水平的降低与 Ki67 和 CD105 表达的降低以及 caspase-3 的增加密切相关。二甲双胍还影响 OPN 的循环水平,这是通过二甲双胍的全身和局部作用发现的。该结果是有关二甲双胍对脂肪干细胞体外影响的宝贵信息来源。
Metformin is applied not only as antidiabetic drug, but also in the treatment of obesity or as antiaging drug. The first part of the research discussed the effect of metformin at concentrations of 1 mM, 5 mM, and 10 mM on the morphology, ultrastructure, and proliferation potential of mice adipose-derived multipotent mesenchymal stromal cells (ASCs) in vitro. Additionally, we determined the influence of metformin on mice adipose tissue metabolism. This study has shown for the first time that metformin inhibits the proliferative potential of ASCs in vitro in a dose- and time-dependent manner. In addition, we have found a significant correlation between the activity of ASCs and osteopontin at the mRNA and protein level. Furthermore, we have demonstrated that 5 mM and 10 mM metformin have cytotoxic effect on ASCs, causing severe morphological, ultrastructural, and apoptotic changes. The reduced level of OPN in the adipose tissue of metformin-treated animals strongly correlated with the lower expression of Ki67 and CD105 and increased caspase-3. The metformin influenced also circulating levels of OPN, which is what was found with systemic and local action of metformin. The results are a valuable source of information regarding the in vitro effect of metformin on adipose-derived stem cells.
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