MicroRNA-9500 attenuates TNF-induced endothelial cells inflammatory damage through inhibition of NF-κB signaling pathway

作者：Jiang, Lei; Zhang, Zhenhai; Li, Zhenfu; Yang, Sumin^*

来源：International Journal of Clinical and Experimental Medicine, 2016, 9(9): 17345-17355.

• microRNA
• TNF
• endothelial cell
• inflammation
• AKT
• NF-kappa B

Background: TNF induces inflammation in endothelial cells (ECs) but the mechanism at post-transcriptional levels is not fully understood. The purpose of this study is to elucidate the post-transcriptional factors regulating TNF-induced injury in HUVECs. Methods: To confirm the predicted miR-9500 is matched with AKT-1, 3'UTR luciferase activity of AKT-1 was used to assess. Then, HUVECs were exposed to TNF in the presence or absence of miR-9500, its mimics or inhibitors. The NF-kappa B signaling pathway is involved in TNF-induced chronic EC inflammation was investigated. Results: Luciferase reporter analysis showed that miR-9500 over-expression leads to decreased activity of luciferase gene fused with AKT1 3'-UTR as well as reduced AKT-1 expression in human HUVECs. Therefore, AKT-1 is direct targets of miR-9500. TNF resulted in markedly increased the up-expression of MMP-9, sICAM-1, and intercellular adhesion molecule 1 (ICAM-1) in HUVECS, whereas miR-9500 reduced expression of MMP-9, ICAM-1, and sICAM-1. Furthermore, miR-9500 substantially attenuated TNF-induced up-regulation expression of AKT-1 and NF-kappa B in HUVECs, respectively. But transfection with inhibitors of miR-9500, antagomiR-9500, overtly accentuated TNF-induced up-expression level of AKT-1 and NF-beta B in HUVECs. MiR-9500 exerts effects on cell proliferation or viability of HUVECS, and accentuates caspase-dependent apoptosis. Conclusions: We identified miR-9500, which specifically bind to AKT1 mRNA 3'-UTR. MiR-9500 is a crucial mediator of endothelial inflammatory damage, and regulating expression of ICAM-1, sICAM-1, and MMP-9 at post-transcriptional levels, protecting against endothelial inflammatory damage through inhibiting the NF-kappa B signaling pathway. Moreover, it exerts effects on controlling viability and apoptosis of HUVECS. Our findings suggest that targeting miR-9500, being involved in chronic EC inflammation, is a promising strategy for the prevention and treatment of chronic inflammation associated diseases, including non-healing wound.

• 出版日期2016
• 单位青岛大学; 中国人民解放军陆军总医院