Targeted ablation of miR-21 decreases murine eosinophil progenitor cell growth.
Targeted ablation of miR-21 decreases murine eosinophil progenitor cell growth.
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DOI：
10.1371/journal.pone.0059397
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Rothenberg ME
中科院分区：
文献类型：
--
作者：
Lu TX;Lim EJ;Itskovich S;Besse JA;Plassard AJ;Mingler MK;Rothenberg JA;Fulkerson PC;Aronow BJ;Rothenberg ME
MiR-21是与嗜酸性粒细胞增多症相关的多种过敏性疾病中上调最多的mirna之一，并已被证明与嗜酸性粒细胞水平呈正相关。在此，我们发现miR-21在il -5驱动的嗜酸性粒细胞从祖细胞向体外分化过程中上调。靶向消融miR-21导致嗜酸性粒细胞祖细胞生长减少。此外，与miR-21+/+嗜酸性粒细胞祖细胞相比，膜联蛋白V阳性水平升高表明，miR-21−/−嗜酸性粒细胞祖细胞凋亡增加。事实上，miR-21−/−小鼠体内的血嗜酸性粒细胞水平降低，骨髓中嗜酸性粒细胞集落形成单位容量降低。通过基因表达微阵列分析，我们发现参与细胞增殖（e,g, Ms4a3, Grb7）、细胞周期和免疫反应的基因失调是miR-21在嗜酸性粒细胞祖细胞中影响的最重要的途径。这些结果表明，miR-21可以通过影响嗜酸性粒细胞祖细胞的生长来调节嗜酸性粒细胞的发育。我们的发现已经确定了第一个在调节嗜酸性粒细胞发育中起作用的mirna之一。
MiR-21 is one of the most up-regulated miRNAs in multiple allergic diseases associated with eosinophilia and has been shown to positively correlate with eosinophil levels. Herein, we show that miR-21 is up-regulated during IL-5-driven eosinophil differentiation from progenitor cells in vitro. Targeted ablation of miR-21 leads to reduced eosinophil progenitor cell growth. Furthermore, miR-21−/− eosinophil progenitor cells have increased apoptosis as indicated by increased levels of annexin V positivity compared to miR-21+/+ eosinophil progenitor cells. Indeed, miR-21−/− mice have reduced blood eosinophil levels in vivo and reduced eosinophil colony forming unit capacity in the bone marrow. Using gene expression microarray analysis, we identified dysregulation of genes involved in cell proliferation (e,g, Ms4a3, Grb7), cell cycle and immune response as the most significant pathways affected by miR-21 in eosinophil progenitors. These results demonstrate that miR-21 can regulate the development of eosinophils by influencing eosinophil progenitor cell growth. Our findings have identified one of the first miRNAs with a role in regulating eosinophil development.
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DOI：
10.4049/jimmunol.0803560
发表时间：
2009-04-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lu TX;Munitz A;Rothenberg ME
通讯作者：
Rothenberg ME
DOI：
10.4049/jimmunol.1101235
发表时间：
2011-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lu TX;Hartner J;Lim EJ;Fabry V;Mingler MK;Cole ET;Orkin SH;Aronow BJ;Rothenberg ME
通讯作者：
Rothenberg ME
影响因子：
15.9
作者：
Donato, JL;Ko, J;Adra, CN
通讯作者：
Adra, CN
影响因子：
5.5
作者：
Rosas, Marcela;Dijkers, Pascale F.;Coffer, Paul J.
通讯作者：
Coffer, Paul J.
影响因子：
14.9
作者：
Chen J;Bardes EE;Aronow BJ;Jegga AG
通讯作者：
Jegga AG