MicroRNA-let-7a expression is increased in the mesangial cells of NZB/W mice and increases IL-6 production in vitro.
MicroRNA-let-7a expression is increased in the mesangial cells of NZB/W mice and increases IL-6 production in vitro.
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MicroRNA-LET-7A表达在NZB/W小鼠的肾小球细胞中增加，并在体外增加IL-6产生。
DOI：
10.3109/08916934.2013.773976
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发表时间：
2013-09
期刊：
影响因子：
3.5
通讯作者：
Reilly CM
中科院分区：
文献类型：
--
作者：
Chafin CB;Regna NL;Dai R;Caudell DL;Reilly CM
最近的证据支持系统性红斑狼疮（SLE）的发病机制中的表观遗传学改变的作用。microRNA（miRNAs或miRs）是内源性表观遗传调节因子，其表达在许多疾病（包括SLE）中改变。IL-6是狼疮性肾炎（LN）期间由系膜细胞产生的一种炎症细胞因子。IL-6的3′非翻译区（UTR）含有miRNA-let-7a（let-7a）的潜在结合位点。我们发现，与年龄匹配的新西兰白色（NZW）小鼠相比，在患病前和活动性患病的新西兰黑色/白色（NZB/W）小鼠的系膜细胞中let-7a表达显著增加。let-7a的过表达在体外刺激的系膜细胞中增加IL-6的产生，与未转染的对照相比。let-7a的抑制没有显著影响免疫刺激的IL-6产生。当用转录抑制剂放线菌素D（ActD）处理过表达let-7a的刺激系膜细胞时，IL-6降解更快，这与let-7a直接靶向IL-6的3′ UTR一致。let-7a的过表达增加了tristetraprolin（TTP）的表达，TTP是一种RNA结合蛋白（RBP），在IL-6的3′ UTR中具有5个潜在的结合区域。ActD抑制蛋白质的转录，包括TTP，这可能有助于let-7a介导的免疫刺激的IL-6产生的增加。这些数据表明，NZB/W小鼠具有比NZW小鼠更高的let-7a表达，并且体外let-7a表达的增加增加了受刺激的系膜细胞中的IL-6产生。进一步研究let-7a表达在炎症中的作用是必要的。
Recent evidence supports a role for epigenetic alterations in the pathogenesis of systemic lupus erythematosus (SLE). MicroRNAs (miRNAs or miRs) are endogenous epigenetic regulators whose expression is altered in many diseases, including SLE. IL-6 is an inflammatory cytokine produced by mesangial cells during lupus nephritis (LN). IL-6 contains a potential binding site for miRNA-let-7a (let-7a) in its 3′ untranslated region (UTR). We found let-7a expression was significantly increased in the mesangial cells of pre-diseased and actively diseased New Zealand Black/White (NZB/W) mice compared to age-matched New Zealand White (NZW) mice. Overexpression of let-7a in vitro increased IL-6 production in stimulated mesangial cells compared to non-transfected controls. Inhibition of let-7a did not significantly affect immune-stimulated IL-6 production. When stimulated mesangial cells overexpressing let-7a were treated with the transcription inhibitor Actinomycin D (ActD), IL-6 was degraded faster, consistent with the direct targeting of the 3′ UTR of IL-6 by let-7a. Overexpression of let-7a increased the expression of tristetraprolin (TTP), an RNA-binding protein (RBP) that has 5 potential binding regions in the 3′ UTR of IL-6. ActD inhibited the transcription of proteins including TTP that may contribute to the let-7a-mediated increase in immune-stimulated IL-6 production. These data show that NZB/W mice have higher let-7a expression than NZW mice and that increased let-7a expression in vitro increases IL-6 production in stimulated mesangial cells. Further studies examining the role of let-7a expression in inflammation are warranted.
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DOI：
10.4049/jimmunol.1002218
发表时间：
2011-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Divekar AA;Dubey S;Gangalum PR;Singh RR
通讯作者：
Singh RR
影响因子：
3.7
作者：
Chege, Duncan;Chai, Yijie;Rebbapragada, Anuradha
通讯作者：
Rebbapragada, Anuradha
影响因子：
2.6
作者：
Dai, Y.;Huang, Y-S;Yin, Y-B
通讯作者：
Yin, Y-B
影响因子：
14.9
作者：
Al-Haj L;Blackshear PJ;Khabar KS
通讯作者：
Khabar KS
DOI：
10.4049/jimmunol.0803646
发表时间：
2009-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Collison LW;Pillai MR;Chaturvedi V;Vignali DA
通讯作者：
Vignali DA