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Bcl-2 和 Bcl-Xl 在人骨髓间充质干细胞分化过程中凋亡的不同作用。

Distinct roles of Bcl-2 and Bcl-Xl in the apoptosis of human bone marrow mesenchymal stem cells during differentiation.

机构信息

INSERM, UMR 892, Équipe Labellisée Ligue contre le Cancer, Nantes, France.

出版信息

PLoS One. 2011 May 12;6(5):e19820. doi: 10.1371/journal.pone.0019820.

DOI:10.1371/journal.pone.0019820
PMID:21589877
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3093403/
Abstract

BACKGROUND

Adult mesenchymal stem cells (MSCs) can be maintained over extended periods of time before activation and differentiation. Little is known about the programs that sustain the survival of these cells.

PRINCIPAL FINDINGS

Undifferentiated adult human MSCs (hMSCs) did not undergo apoptosis in response to different cell death inducers. Conversely, the same inducers can readily induce apoptosis when hMSCs are engaged in the early stages of differentiation. The survival of undifferentiated cells is linked to the expression of Bcl-Xl and Bcl-2 in completely opposite ways. Bcl-Xl is expressed at similar levels in undifferentiated and differentiated hMSCs while Bcl-2 is expressed only in differentiated cells. In undifferentiated hMSCs, the down-regulation of Bcl-Xl is associated with an increased sensitivity to apoptosis while the ectopic expression of Bcl-2 induced apoptosis. This apoptosis is linked to the presence of cytoplasmic Nur 77 in undifferentiated hMSCs.

SIGNIFICANCE

In hMSCs, the expression of Bcl-2 depends on cellular differentiation and can be either pro- or anti-apoptotic. Bcl-Xl, on the other hand, exhibits an anti-apoptotic activity under all conditions.

摘要

背景

成体间充质干细胞(MSCs)在激活和分化之前可以长时间维持。关于维持这些细胞存活的程序知之甚少。

主要发现

未分化的成人人类间充质干细胞(hMSCs)不会对不同的细胞死亡诱导剂产生凋亡反应。相反,当 hMSCs 处于早期分化阶段时,相同的诱导剂可以很容易地诱导凋亡。未分化细胞的存活与 Bcl-Xl 和 Bcl-2 的表达以完全相反的方式相关联。Bcl-Xl 在未分化和分化的 hMSCs 中的表达水平相似,而 Bcl-2 仅在分化细胞中表达。在未分化的 hMSCs 中,Bcl-Xl 的下调与对凋亡的敏感性增加有关,而 Bcl-2 的异位表达则诱导凋亡。这种凋亡与细胞质 Nur 77 在未分化的 hMSCs 中的存在有关。

意义

在 hMSCs 中,Bcl-2 的表达取决于细胞分化,可以是促凋亡或抗凋亡。另一方面,Bcl-Xl 在所有情况下均表现出抗凋亡活性。

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