Survival of hypoxic human mesenchymal stem cells is enhanced by a positive feedback loop involving miR-210 and hypoxia-inducible factor 1.

Survival of hypoxic human mesenchymal stem cells is enhanced by a positive feedback loop involving miR-210 and hypoxia-inducible factor 1.
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DOI:
10.4142/jvs.2013.14.1.69
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发表时间:
2013
影响因子:
1.8
通讯作者:
Chung YA
Chung YA
中科院分区:
农林科学4区
文献类型:
--
作者:
Chang W;Lee CY;Park JH;Park MS;Maeng LS;Yoon CS;Lee MY;Hwang KC;Chung YA

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使用间充质干细胞(MSCs)已成为一种潜在的治疗心肌梗死的新方法。然而,移植后MSCs的生存能力差严重限制了这种新策略的有效性。microRNA-210 (miR-210)的表达是由缺氧诱导的,对缺氧条件下的细胞存活至关重要。缺氧可增加人间充质干细胞(hMSCs)中缺氧诱导因子-1 (HIF-1)蛋白和miR-210的水平。miR-210正调控HIF-1α活性。此外,缺氧也通过HIF-1α的调控诱导miR-210的表达。为了研究miR-210对缺氧条件下hMSC存活的影响,我们在过表达miR-210或缺乏HIF-1α表达的hMSCs中评估了存活率以及与细胞存活相关的信号。在缺氧的hMSCs中,miR-210表达升高可提高存活率以及Akt和ERK活性。这些数据表明,涉及miR-210和HIF-1α的正反馈回路对缺氧条件下的MSC存活很重要。
The use of mesenchymal stem cells (MSCs) has emerged as a potential new treatment for myocardial infarction. However, the poor viability of MSCs after transplantation critically limits the efficacy of this new strategy. The expression of microRNA-210 (miR-210) is induced by hypoxia and is important for cell survival under hypoxic conditions. Hypoxia increases the levels of hypoxia inducible factor-1 (HIF-1) protein and miR-210 in human MSCs (hMSCs). miR-210 positively regulates HIF-1α activity. Furthermore, miR-210 expression is also induced by hypoxia through the regulation of HIF-1α. To investigate the effect of miR-210 on hMSC survival under hypoxic conditions, survival rates along with signaling related to cell survival were evaluated in hMSCs over-expressing miR-210 or ones that lacked HIF-1α expression. Elevated miR-210 expression increased survival rates along with Akt and ERK activity in hMSCs with hypoxia. These data demonstrated that a positive feedback loop involving miR-210 and HIF-1α was important for MSC survival under hypoxic conditions.
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