Stromal cell-derived factor-1β mediates cell survival through enhancing autophagy in bone marrow-derived mesenchymal stem cells.
Stromal cell-derived factor-1β mediates cell survival through enhancing autophagy in bone marrow-derived mesenchymal stem cells.
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DOI：
10.1371/journal.pone.0058207
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hill WD
中科院分区：
文献类型：
--
作者：
Herberg S;Shi X;Johnson MH;Hamrick MW;Isales CM;Hill WD
骨髓间充质干/基质细胞（BMSCs）在细胞治疗方面具有巨大的潜力，但其治疗效果仍不确定。移植的BMSC通常不能在骨髓（BM）内植入，部分原因是供体细胞响应于炎症反应、缺氧、氧化应激或营养饥饿而存活不良。两个基本的细胞过程，细胞凋亡和自噬，可能是负责受损的移植BMSCs的生存。然而，细胞凋亡和自噬在BMSC稳态中的功能关系是复杂的，并且还没有很好地理解。基质细胞衍生因子-1（SDF-1）/CXC趋化因子受体4（CXCR 4）信号传导轴似乎通过改善细胞增殖和存活来维持BM干细胞群的增殖和存活，以应对应激;然而，确切的机制仍不清楚。我们最近描述了一种新型的基因工程Tet-Off-SDF-1β BMSCs，其在强力霉素的严格控制下过表达SDF-1β，从而为研究SDF-1β的孤立作用提供了理想的模型系统。在这项研究中，我们验证了SDF-1β可以通过增加自噬介导体外BMSCs细胞存活的假设。我们发现SDF-1β对BMSC增殖没有影响;然而，SDF-1β通过增加自噬和减少caspase-3依赖的凋亡，显著保护基因工程BMSC免受H2 O2诱导的细胞死亡。综上所述，我们提供了新的证据，SDF-1/CXCR 4轴，特别是由SDF-1β亚型激活，通过增加自噬在氧化应激下调节BMSC存活中起着关键作用。
Bone marrow-derived mesenchymal stem/stromal cells (BMSCs) hold great potential for cell-based therapy, yet the therapeutic efficacy remains uncertain. Transplanted BMSCs often fail to engraft within the bone marrow (BM), in part due to the poor survival of donor cells in response to inflammatory reactions, hypoxia, oxidative stress, or nutrient starvation. Two basic cell processes, apoptosis and autophagy, could potentially be responsible for the impaired survival of transplanted BMSCs. However, the functional relationship between apoptosis and autophagy in BMSC homeostasis is complex and not well understood. The stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) signaling axis appears to be critical in maintaining proliferation and survival of BM stem cell populations through improving cell proliferation and survival in response to stress; however, the exact mechanisms remain unclear. We recently described novel genetically engineered Tet-Off-SDF-1β BMSCs, which over-express SDF-1β under tight doxycycline-control, thus providing an ideal model system to investigate the isolated effects of SDF-1β. In this study we tested the hypothesis that SDF-1β can mediate cell survival of BMSCs in vitro through increasing autophagy. We found that SDF-1β had no effect on BMSC proliferation; however, SDF-1β significantly protected genetically engineered BMSCs from H2O2-induced cell death through increasing autophagy and decreasing caspase-3-dependent apoptosis. Taken together, we provide novel evidence that the SDF-1/CXCR4 axis, specifically activated by the SDF-1β isoform, plays a critical role in regulating BMSC survival under oxidative stress through increasing autophagy.
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影响因子：
13.3
作者：
Maiuri, Maria Chiara;Criollo, Alfredo;Kroemer, Guido
通讯作者：
Kroemer, Guido
影响因子：
20.3
作者：
Davis, DA;Singer, KE;Tosato, G
通讯作者：
Tosato, G
影响因子：
11.8
作者：
Lipinski, Marta M.;Hoffman, Greg;Ng, Aylwin;Zhou, Wen;Py, Benedicte F.;Hsu, Emily;Liu, Xuxin;Eisenberg, Jason;Liu, Jun;Blenis, John;Xavier, Ramnik J.;Yuan, Junying
通讯作者：
Yuan, Junying
影响因子：
9.7
作者：
Kessel, David;Reiners, John J., Jr.
通讯作者：
Reiners, John J., Jr.
DOI：
10.1073/pnas.132252399
发表时间：
2002-06-25
影响因子：
11.1
作者：
Horwitz, EM;Gordon, PL;Hofmann, T
通讯作者：
Hofmann, T