MicroRNA-26a modulates transforming growth factor beta-1-induced proliferation in human fetal lung fibroblasts
MicroRNA-26a modulates transforming growth factor beta-1-induced proliferation in human fetal lung fibroblasts
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MicroRNA-26a 调节转化生长因子 β-1 诱导的人胎肺成纤维细胞增殖
DOI：
10.1016/j.bbrc.2014.10.106
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发表时间：
2014-11-28
影响因子：
3.1
通讯作者：
Wen, Fuqiang
中科院分区：
文献类型：
--
作者：
Li, Xiaoou;Liu, Lian;Wen, Fuqiang
microRNA -26a是一种新发现的具有较强抗肿瘤能力的microRNA，能够抑制细胞增殖，激活肿瘤特异性凋亡。然而，miR-26a是否能抑制肺成纤维细胞的过度生长尚不清楚。本研究探讨miR-26a与肺纤维化的关系。我们首先研究了miR-26a对接受或不接受tgf - β治疗的人肺成纤维细胞增殖活性的影响。我们发现内源性miR-26a的抑制促进了增殖，成熟miR-26a的恢复抑制了人肺成纤维细胞的增殖。我们还研究了miR-26a可以通过直接靶向CCND2的3'-UTR来阻断G1/S期转变，降解mRNA并降低Cyclin D2的蛋白表达。此外，我们发现miR-26a介导tgf - β 2- tgf - β 1反馈回路并抑制tgf - β r1激活。此外，miR-26a的过表达也显著抑制了tgf - β 1相互作用- ctgf -胶原纤维化通路。综上所述，我们的研究表明miR-26a在tgf - β诱导的人肺成纤维细胞增殖的抗纤维化机制中发挥重要作用，通过直接靶向Cyclin D2，调节tgf - β R I和tgf - β 2，并提示miR-26a在改善肺纤维化方面的治疗潜力。(C) 2014爱思唯尔公司版权所有。
MicroRNA-26a is a newly discovered microRNA that has a strong anti-tumorigenic capacity and is capable of suppressing cell proliferation and activating tumor-specific apoptosis. However, whether miR-26a can inhibit the over-growth of lung fibroblasts remains unclear. The relationship between miR-26a and lung fibrosis was explored in the current study. We first investigated the effect of miR-26a on the proliferative activity of human lung fibroblasts with or without TGF-betal treatment. We found that the inhibition of endogenous miR-26a promoted proliferation and restoration of mature miR-26a inhibited the proliferation of human lung fibroblasts. We also examined that miR-26a can block the G1/S phase transition via directly targeting 3'-UTR of CCND2, degrading mRNA and decreasing protein expression of Cyclin D2. Furthermore, we showed that miR-26a mediated a TGF-beta 2-TGF-beta 1 feedback loop and inhibited TGF-beta R I activation. In addition, the overexpression of miR-26a also significantly suppressed the TGF-beta 1-interacting-CTGF-collagen fibrotic pathway. In summary, our studies indicated an essential role of miR-26a in the anti-fibrotic mechanism in TGF-betal-induced proliferation in human lung fibroblasts, by directly targeting Cyclin D2, regulating TGF-beta R I as well as TGF-beta 2, and suggested the therapeutic potential of miR-26a in ameliorating lung fibrosis. (C) 2014 Elsevier Inc. All rights reserved.