High glucose induces adipogenic differentiation of muscle-derived stem cells
High glucose induces adipogenic differentiation of muscle-derived stem cells
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DOI：
10.1073/pnas.0711402105
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发表时间：
2008-01-29
影响因子：
11.1
通讯作者：
Rizzuto, Rosario
中科院分区：
文献类型：
--
作者：
Aguiari, Paola;Leo, Sara;Rizzuto, Rosario
间充质组织的再生依赖于常驻干细胞群体，在大多数情况下，在细胞身份和分化信号方面仍然难以捉摸。我们在这里表明，原代细胞培养来源于脂肪组织或骨骼肌分化成脂肪细胞培养时，在高葡萄糖。高糖诱导ROS产生和PKC β激活。这两个事件出现在这个分化过程中的关键步骤，可以直接由氧化剂诱导和抑制PKC β siRNA沉默。分化的脂肪细胞，当植入体内时，形成活的和血管化的脂肪组织。总体而言，这些数据强调了高葡萄糖触发的一种以前未表征的分化途径，该途径不仅驱动脂肪组织中的驻留干细胞，还驱动肌肉细胞中存在的未定型前体细胞形成脂肪库。这一过程可能代表了肥胖和胰岛素抵抗之间的前馈循环，在糖尿病的发病机制中起着关键作用。
Regeneration of mesenchymal tissues depends on a resident stem cell population, that in most cases remains elusive in terms of cellular identity and differentiation signals. We here show that primary cell cultures derived from adipose tissue or skeletal muscle differentiate into adipocytes when cultured in high glucose. High glucose induces ROS production and PKC beta activation. These two events appear crucial steps in this differentiation process that can be directly induced by oxidizing agents and inhibited by PKC beta siRNA silencing. The differentiated adipocytes, when implanted in vivo, form viable and vascularized adipose tissue. Overall, the data highlight a previously un-characterized differentiation route triggered by high glucose that drives not only resident stem cells of the adipose tissue but also uncommitted precursors present in muscle cells to form adipose depots. This process may represent a feed-forward cycle between the regional increase in adiposity and insulin resistance that plays a key role in the pathogenesis of diabetes mellitus.