Liu Xiangde, Nelson Amy, Wang Xingqi, Kanaji Nobuhiro, Kim Miok, Sato Tadashi, Nakanishi Masanori, Li YingJi, Sun Jianhong, Michalski Joel, Patil Amol, Basma Hesham, Rennard Stephen I
Pulmonary, Critical Care, Sleep and Allergy Medicine, Department of Internal Medicine, University of Nebraska Medical Center, 985885 Nebraska Medical Center, Omaha, NE 68198-5885, USA.
Biochem Biophys Res Commun. 2009 Feb 27;380(1):177-82. doi: 10.1016/j.bbrc.2009.01.066. Epub 2009 Jan 22.
MicroRNA plays an important role in cell differentiation, proliferation and cell death. The current study found that miRNA-146a was up-regulated in human bronchial epithelial cells (HBECs) in response to stimulation by TGF-beta1 plus cytomix (a mixture of IL-1beta, IFN-gamma and TNF-alpha). TGF-beta1 plus cytomix (TCM) induced apoptosis in HBECs (3.4+/-0.6% of control vs 83.1+/-4.0% of TCM treated cells, p<0.01), and this was significantly blocked by the miRNA-146a mimic (8.8+/-1.5%, p<0.01). In contrast, a miRNA-146a inhibitor had only a modest effect on cell survival but appeared to augment the induction of epithelial-mesenchymal transition (EMT) in response to the cytokines. The MicroRNA-146a mimic appears to modulate HBEC survival through a mechanism of up-regulating Bcl-XL and STAT3 phosphorylation, and by this mechanism it could contribute to tissue repair and remodeling.
微小RNA在细胞分化、增殖和细胞死亡中发挥着重要作用。当前研究发现，在转化生长因子β1（TGF-β1）加细胞混合因子（白细胞介素-1β、干扰素-γ和肿瘤坏死因子-α的混合物）刺激下，人支气管上皮细胞（HBECs）中的微小RNA-146a上调。TGF-β1加细胞混合因子（TCM）诱导HBECs凋亡（对照组为3.4±0.6%，而经TCM处理的细胞为83.1±4.0%，p<0.01），而微小RNA-146a模拟物可显著阻断这种凋亡（8.8±1.5%，p<0.01）。相反，微小RNA-146a抑制剂对细胞存活仅有适度影响，但似乎会增强细胞因子诱导的上皮-间质转化（EMT）。微小RNA-146a模拟物似乎通过上调Bcl-XL和信号转导及转录激活因子3（STAT3）磷酸化的机制来调节HBECs的存活，通过这种机制它可能有助于组织修复和重塑。
