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在体外和体内,PPARγ的激活通过上调miR-124来抑制促炎细胞因子的产生。

Activation of PPARγ inhibits pro-inflammatory cytokines production by upregulation of miR-124 in vitro and in vivo.

作者信息

Wang Dan, Shi Liuyan, Xin Wei, Xu Jiancheng, Xu Jing, Li Qi, Xu Zhi, Wang Jianchun, Wang Guansong, Yao Wei, He Binfeng, Yang Yu, Hu Mingdong

机构信息

Department of Respiratory Medicine, Respiratory Research Institute, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China.

Department of Scientific Research and Education, The Affiliated Baoji Hospital, Xi'an Medical University, Baoji 721006, China.

出版信息

Biochem Biophys Res Commun. 2017 May 6;486(3):726-731. doi: 10.1016/j.bbrc.2017.03.106. Epub 2017 Mar 22.

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) and miR-124 have been reported to play important roles in regulation of inflammation. However, the underlying anti-inflammatory mechanisms remain not well understood. In the present study, we demonstrated that the expression level of PPARγ is positively correlated with that of miR-124 in patients with sepsis. Activation of PPARγ upregulates miR-124 and in turn inhibits miR-124 target gene. PPARγ bound directly to PPRE in the miR-124 promoter region, and enhanced the promoter transcriptional activity. PPARγ-induced miR-124 is involved in the suppression of pro-inflammatory cytokine in vitro and in vivo. These results suggest that PPARγ-induced miR-124 inhibits the production of pro-inflammatory cytokines is a novel PPARγ anti-inflammatory mechanism and also indicate that miR-124 may be a potential therapeutic target for the treatment of inflammatory diseases.

摘要

据报道,过氧化物酶体增殖物激活受体γ(PPARγ)和miR-124在炎症调节中发挥重要作用。然而,其潜在的抗炎机制仍未完全清楚。在本研究中,我们证明脓毒症患者中PPARγ的表达水平与miR-124的表达水平呈正相关。PPARγ的激活上调miR-124,进而抑制miR-124靶基因。PPARγ直接与miR-124启动子区域的PPRE结合,并增强启动子转录活性。PPARγ诱导的miR-124在体外和体内均参与促炎细胞因子的抑制。这些结果表明,PPARγ诱导的miR-124抑制促炎细胞因子的产生是一种新的PPARγ抗炎机制,也表明miR-124可能是治疗炎症性疾病的潜在治疗靶点。

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