南蛇藤抑制幽门螺杆菌诱导的胃上皮细胞上皮间质转化及靶向 miR-21/PDCD4 信号通路对炎症反应的影响。

Effect of Celastrus orbiculatus in inhibiting Helicobacter pylori induced inflammatory response by regulating epithelial mesenchymal transition and targeting miR-21/PDCD4 signaling pathway in gastric epithelial cells.

机构信息

Chinese Integrative Medicine Oncology Department, First Affiliated Hospital of Medical University of Anhui, Hefei, 230000, Anhui, China.

General Surgery Department, First Affiliated Hospital of Medical University of Anhui, Hefei, 230000, Anhui, China.

出版信息

BMC Complement Altern Med. 2019 Apr 29;19(1):91. doi: 10.1186/s12906-019-2504-x.

BACKGROUND

The extract of Celastrus orbiculatus (COE) have been studied for anti-Helicobacter pylori (H. pylori) activity and anti-cancer effects in vitro and in vivo. However, the molecular mechanism by which COE inhibits H. pylori-induced inflammatory response has not been fully elucidated so far.

METHODS

The effects of COE on viability, morphological changes, inflammatory cytokine secretion, protein and mRNA expression were analyzed by MTT assay, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, western blot and real-time PCR (RT-PCR), respectively. The methylation level of programmed cell death 4 (PDCD4) promoter was investigated by methylation-specific PCR. (MSP) .

RESULTS

COE effectively inhibited the H.pylori-induced inflammatory response by regulating epithelial-mesenchymal transition (EMT). The methylation level of PDCD4 promoter was suppressed by COE, which increased the expression ofPDCD4. Moreover, COE could inhibit microRNA-21 (miR-21) expression, as shown by an enhancement of its target gene PDCD4. Furthermore, both miR-21 over-expression and PDCD4 silencing attenuated the anti-inflammatory effect. of COE.

CONCLUSIONS

COE inhibits H. pylori induced inflammatory response through regulating EMT, correlating with inhibition of miR-21/PDCD4 signal pathways in gastric epithelial cells.

背景

南蛇藤提取物（COE）已在体外和体内研究其抗幽门螺杆菌（H. pylori）活性和抗癌作用。然而，迄今为止，COE 抑制 H. pylori 诱导的炎症反应的分子机制尚未完全阐明。

方法

通过 MTT 测定、酶联免疫吸附测定（ELISA）、免疫荧光、western blot 和实时 PCR（RT-PCR）分别分析 COE 对细胞活力、形态变化、炎性细胞因子分泌、蛋白和 mRNA 表达的影响。通过甲基化特异性 PCR（MSP）研究程序性细胞死亡因子 4（PDCD4）启动子的甲基化水平。

结果

COE 通过调节上皮-间充质转化（EMT）有效抑制 H.pylori 诱导的炎症反应。COE 抑制 PDCD4 启动子的甲基化水平，从而增加 PDCD4 的表达。此外，COE 可以抑制 microRNA-21（miR-21）的表达，表现为其靶基因 PDCD4 的增强。此外，miR-21 过表达和 PDCD4 沉默均减弱了 COE 的抗炎作用。