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骨髓间充质干细胞中的 KATP 通道:成骨分化时 Kir6.2 亚基的强烈上调。

KATP channels in mesenchymal stromal stem cells: strong up-regulation of Kir6.2 subunits upon osteogenic differentiation.

机构信息

Department of Medicine V, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.

出版信息

Tissue Cell. 2011 Oct;43(5):331-6. doi: 10.1016/j.tice.2011.06.004. Epub 2011 Aug 5.

DOI:10.1016/j.tice.2011.06.004
PMID:21820692
Abstract

The promising use of mesenchymal stromal cells (MSC) in regenerative technologies accounts for necessity of detailed study of their physiology. Proliferation and differentiation of multipotent cells often involve changes in their metabolic state. In the present study, we analyzed the expression of ATP-sensitive potassium (K(ATP)) channels in MSC and upon in vitro differentiation. K(ATP) channels are present in many cells and regulate a variety of cellular functions by coupling cell metabolism with membrane potential. Kir6.1, Kir6.2 and SUR2A were expressed in undifferentiated MSC, whereas SUR2B and SUR1 were not detected on cDNA and protein level. Upon adipogenic differentiation Kir6.1 and SUR2A showed a significant reduction of the amount of mRNA by 84% and 95%, respectively, whereas Kir6.2 expression was unchanged. Osteogenic differentiation strongly up-regulated Kir6.2 mRNA (28-fold) whereas Kir6.1 and SUR2A showed no significant change in expression. Quantitative Western blot analysis and immunofluorescence staining confirmed the elevated expression of Kir6.2 upon osteogenic differentiation. Taken together, expression changes of K(ATP) channels may contribute to in vitro differentiation of MSC and represent changes in the metabolic state of the developing tissue.

摘要

间充质基质细胞(MSC)在再生技术中的应用前景,使得对其生理学进行详细研究成为必要。多能细胞的增殖和分化通常涉及到其代谢状态的变化。在本研究中,我们分析了 MSC 及其体外分化过程中 ATP 敏感性钾(K(ATP))通道的表达。K(ATP) 通道存在于许多细胞中,通过将细胞代谢与膜电位偶联来调节多种细胞功能。在未分化的 MSC 中表达了 Kir6.1、Kir6.2 和 SUR2A,而 cDNA 和蛋白水平均未检测到 SUR2B 和 SUR1。在成脂分化过程中,Kir6.1 和 SUR2A 的 mRNA 量分别显著减少了 84%和 95%,而 Kir6.2 的表达则保持不变。成骨分化强烈地上调了 Kir6.2 mRNA(28 倍),而 Kir6.1 和 SUR2A 的表达则没有明显变化。定量 Western blot 分析和免疫荧光染色证实了成骨分化时 Kir6.2 的表达上调。总之,K(ATP)通道的表达变化可能有助于 MSC 的体外分化,并代表了发育组织代谢状态的变化。

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