MicroRNA-Mediated Down-Regulation of Apoptosis Signal-Regulating Kinase 1 (ASK1) Attenuates the Apoptosis of Human Mesenchymal Stem Cells (MSCs) Transplanted into Infarcted Heart.
MicroRNA-Mediated Down-Regulation of Apoptosis Signal-Regulating Kinase 1 (ASK1) Attenuates the Apoptosis of Human Mesenchymal Stem Cells (MSCs) Transplanted into Infarcted Heart.
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DOI：
10.3390/ijms17101752
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发表时间：
2016-10-20
影响因子：
5.6
通讯作者：
Hwang KC
中科院分区：
文献类型：
--
作者：
Lee CY;Shin S;Lee J;Seo HH;Lim KH;Kim H;Choi JW;Kim SW;Lee S;Lim S;Hwang KC
使用成体干细胞（如间充质干细胞（MSC））的干细胞疗法在治疗受损心脏方面取得了一些有希望的结果。然而，骨髓间充质干细胞移植后存活率低仍然是限制干细胞治疗效果的关键因素之一。在受损的心脏中，由于活性氧（ROS）产生的氧化应激可导致移植的MSC死亡。细胞凋亡信号调节激酶1（ASK 1）与氧化应激相关病理状况的发展有关。因此，我们假设下调人类间充质干细胞（hMSCs）中的ASK 1可能会减弱间充质干细胞移植后的死亡。为了验证这一假设，我们根据miRNA靶点预测数据库和经验数据筛选了microRNAs（miRNAs），并研究了所选miRNAs对人脂肪源性干细胞（hASC）和大鼠心肌梗死（MI）模型的抗凋亡作用。我们的数据表明，miRNA-301 a最显著地抑制hASCs中的ASK 1表达。在暴露于缺氧条件下的富含miRNA-301 a的hASCs中，凋亡相关基因显著下调。总之，这些数据表明，miRNA介导的ASK 1下调在移植后保护MSC，导致基于MSC的细胞疗法的功效增加。
Stem cell therapy using adult stem cells, such as mesenchymal stem cells (MSCs) has produced some promising results in treating the damaged heart. However, the low survival rate of MSCs after transplantation is still one of the crucial factors that limit the therapeutic effect of stem cells. In the damaged heart, oxidative stress due to reactive oxygen species (ROS) production can cause the death of transplanted MSCs. Apoptosis signal-regulating kinase 1 (ASK1) has been implicated in the development of oxidative stress-related pathologic conditions. Thus, we hypothesized that down-regulation of ASK1 in human MSCs (hMSCs) might attenuate the post-transplantation death of MSCs. To test this hypothesis, we screened microRNAs (miRNAs) based on a miRNA-target prediction database and empirical data and investigated the anti-apoptotic effect of selected miRNAs on human adipose-derived stem cells (hASCs) and on rat myocardial infarction (MI) models. Our data indicated that miRNA-301a most significantly suppressed ASK1 expression in hASCs. Apoptosis-related genes were significantly down-regulated in miRNA-301a-enriched hASCs exposed to hypoxic conditions. Taken together, these data show that miRNA-mediated down-regulation of ASK1 protects MSCs during post-transplantation, leading to an increase in the efficacy of MSC-based cell therapy.
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DOI：
10.1046/j.1432-1327.2000.01421.x
发表时间：
2000-06-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Kaltschmidt, B;Kaltschmidt, C;Schmitz, ML
通讯作者：
Schmitz, ML
DOI：
10.1042/bj20101585
发表时间：
2011-03-15
期刊：
The Biochemical journal
影响因子：
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作者：
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通讯作者：
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DOI：
10.1016/j.bbapap.2009.11.002
发表时间：
2010-03-01
影响因子：
3.2
作者：
Bogoyevitch, Marie A.;Ngoei, Kevin R. W.;Ng, Dominic C. H.
通讯作者：
Ng, Dominic C. H.
影响因子：
1.8
作者：
Chang W;Lee CY;Park JH;Park MS;Maeng LS;Yoon CS;Lee MY;Hwang KC;Chung YA
通讯作者：
Chung YA
DOI：
10.1038/mtna.2013.60
发表时间：
2013-10-01
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
通讯作者：
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