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首页> 外文期刊>The journals of gerontology.Series A. Biological sciences and medical sciences >Adipogenic differentiation is impaired in replicative senescent human subcutaneous adipose-derived stromal/progenitor cells
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Adipogenic differentiation is impaired in replicative senescent human subcutaneous adipose-derived stromal/progenitor cells

机译:复制性衰老的人类皮下脂肪来源的基质/祖细胞的成脂分化受到损害

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We demonstrate that adipose-derived stromal/progenitor cells isolated from abdominal subcutaneous fat pads of adult donors successively enter replicative senescence after long-term cultivation. This is characterized by enlarged cell size, flattened morphology, and upregulated senescence-associated β-galactosidase activity. Moreover, the senescence- associated cyclin-dependent kinase inhibitors p16Ink4A and p21Cip1 were induced correlating with activation of the G1/S cell cycle inhibitor retinoblastoma protein and terminal proliferation arrest. The number of cells in the adipose-derived stromal/progenitor cell population with high adipogenic capacity declined inversely with the increase of senescent cells. Adipogenic hormone cocktail induced expression of the adipogenic key regulators peroxisome proliferator-activated receptor-γ2 and CCAAT/enhancer-binding protein α was significantly reduced in senescent adipose-derived stromal/ progenitor cells. Furthermore, the expression of the adipogenic differentiation genes fatty acid binding protein-4, adiponectin, and leptin and the formation of fat droplets were impaired. We conclude cellular senescence contributes to dysfunctions in adipose-derived stromal/progenitor cell replication, adipogenesis, triglyceride storage, and adipokine secretion.
机译:我们证明,从成年供体的腹部皮下脂肪垫分离出的脂肪来源的基质/祖细胞在长期培养后连续进入复制衰老。其特征在于细胞大小增大,形态变平以及衰老相关的β-半乳糖苷酶活性上调。此外,诱导了衰老相关的细胞周期蛋白依赖性激酶抑制剂p16Ink4A和p21Cip1与G1 / S细胞周期抑制剂视网膜母细胞瘤蛋白的激活和终末增殖停滞有关。具有高脂肪形成能力的脂肪来源的基质/祖细胞群中的细胞数目随着衰老细胞的增加而呈反比下降。在衰老脂肪来源的基质/祖细胞中,成脂激素混合物诱导的成脂关键调节因子过氧化物酶体增殖物激活受体-γ2和CCAAT /增强子结合蛋白α的表达显着降低。此外,脂肪形成分化基因脂肪酸结合蛋白4,脂联素和瘦素的表达和脂肪滴的形成受到损害。我们得出结论,细胞衰老是导致脂肪基质细胞/祖细胞复制,脂肪形成,甘油三酸酯存储和脂肪因子分泌功能障碍的原因。

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