MiR-211/STAT5A Signaling Modulates Migration of Mesenchymal Stem Cells to Improve its Therapeutic Efficacy.
MiR-211/STAT5A Signaling Modulates Migration of Mesenchymal Stem Cells to Improve its Therapeutic Efficacy.
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MiR-211/STAT5A 信号传导调节间充质干细胞的迁移以提高其治疗功效。
DOI：
10.1002/stem.2391
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发表时间：
2016-07
期刊：
影响因子：
5.2
通讯作者：
Wang, Jian'an
中科院分区：
文献类型：
--
作者：
Hu, Xinyang;Chen, Panpan;Wu, Yan;Wang, Kan;Xu, Yinchuan;Chen, Han;Zhang, Ling;Wu, Rongrong;Webster, Keith A.;Yu, Hong;Zhu, Wei;Wang, Jian'an
我们前期的研究表明，间充质干细胞（MSCs）移植的治疗效果是通过增强迁移来提高的。microRNA-211（miR-211）可以通过尚未完全理解的机制调节某些细胞类型的迁移特性。本研究旨在探讨miR-211在MSC迁移中的可能作用，以及是否可以使用MSC中miR-211的遗传操作来增强其细胞移植的有益效果。Transwell实验证实miR-211敲低可显著降低MSCs迁移能力，但miR-211过表达可增强MSCs迁移能力。如GFP追踪和SYR基因定量所示，在静脉内移植雄性MSC后2天，miR-211过表达的MSC在雌性大鼠心脏的梗塞周围区域中也表现出显著增加的细胞植入。这使得梗死面积显著减小，心脏功能改善。通过使用基因功能的丧失或获得方法，我们证明了miR-211靶向STAT 5A调节MSC迁移，可能通过与MAPK信号转导相互作用。此外，miR-211过表达在MSC中的有益作用被同时过表达STAT 5A消除，而miR-211沉默对MSC迁移的负面作用被同时下调STAT 5A拯救。最后，使用ChIP-PCR和荧光素酶检测，我们提供了新的证据，STAT 3可以直接结合到启动子元件，激活miR-211的表达。STAT 3/miR-211/STAT 5A信号通路在MSCs迁移中起关键作用。与未修饰的MSC相比，静脉输注过表达miR-211的遗传修饰的MSC可增强对MI后不良重塑的保护。
Our previous study showed that the therapeutic effects of mesenchymal stem cells (MSCs) transplantation were improved by enhancing migration. MicroRNA-211 (miR-211) can modulate the migratory properties of some cell types by mechanisms that are not fully understood. This study was designed to investigate a possible role for miR-211 in MSC migration, and whether genetic manipulation of miR-211 in MSCs could be used to enhance its beneficial effects of cell transplantation. Transwell assays confirmed that MSCs migration of was significantly impaired by miR-211 knockdown but enhanced by miR-211 overexpression. MiR-211 overexpressing MSCs also exhibited significantly increased cell engraftment in the peri-infarct areas of female rat hearts 2 days after intravenous transplantation of male MSCs as shown by GFP tracking and SYR gene quantification. This conferred a significant decrease in infarct size and improved cardiac performance. By using a loss or gain of gene function approach, we demonstrated that miR-211 targeted STAT5A to modulate MSCs migration, possibly by interacting with MAPK signaling. Furthermore, the beneficial effects of miR-211 overexpression in MSCs were abolished by simultaneous overexpression of STAT5A whereas the negative effects of miR-211 silencing on MSC migration were rescued by simultaneous downregulation of STAT5A. Finally, using ChIP-PCR and luciferase assays, we provide novel evidence that STAT3 can directly bind to promoter elements that activate miR-211 expression. STAT3/miR-211/STAT5A signaling plays a key role in MSCs migration. Intravenous infusion of genetically modified miR-211 overexpressing MSCs conveys enhanced protection from adverse post-MI remodeling compared with unmodified MSCs.
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影响因子：
120.7
作者：
Heldman, Alan W.;DiFede, Darcy L.;Fishman, Joel E.;Zambrano, Juan P.;Trachtenberg, Barry H.;Karantalis, Vasileios;Mushtaq, Muzammil;Williams, Adam R.;Suncion, Viky Y.;McNiece, Ian K.;Ghersin, Eduard;Soto, Victor;Lopera, Gustavo;Miki, Roberto;Willens, Howard;Hendel, Robert;Mitrani, Raul;Pattany, Pradip;Feigenbaum, Gary;Oskouei, Behzad;Byrnes, John;Lowery, Maureen H.;Sierra, Julio;Pujol, Mariesty V.;Delgado, Cindy;Gonzalez, Phillip J.;Rodriguez, Jose E.;Bagno, Luiza Lima;Rouy, Didier;Altman, Peter;Foo, Cheryl Wong Po;da Silva, Jose;Anderson, Erica;Schwarz, Richard;Mendizabal, Adam;Hare, Joshua M.
通讯作者：
Hare, Joshua M.
从间充质干细胞释放的肝素酶激活整联蛋白beta1/hif-2alpha/flk-1信号传导，并促进内皮细胞迁移和血管生成。
影响因子：
5.2
作者：
Hu, Xinyang;Zhang, Ling;Jin, Jing;Zhu, Wei;Xu, Yinchuan;Wu, Yan;Wang, Yingchao;Chen, Han;Webster, Keith A.;Chen, Huiqiang;Yu, Hong;Wang, Jian'an
通讯作者：
Wang, Jian'an
影响因子：
10.8
作者：
Haider, Khawaja Husnain;Idris, Niagara Muhammad;Ashraf, Muhammad
通讯作者：
Ashraf, Muhammad
影响因子：
5.2
作者：
Clark, Elizabeth A.;Kalomoiris, Stefanos;Nolta, Jan A.;Fierro, Fernando A.
通讯作者：
Fierro, Fernando A.
影响因子：
24
作者：
Bartunek, Jozef;Behfar, Atta;Terzic, Andre
通讯作者：
Terzic, Andre