LincRNA Cox-2 Regulates Lipopolysaccharide-Induced Inflammatory Response of Human Peritoneal Mesothelial Cells via Modulating miR-21/NF-κB Axis
LincRNA Cox-2 Regulates Lipopolysaccharide-Induced Inflammatory Response of Human Peritoneal Mesothelial Cells via Modulating miR-21/NF-κB Axis
复制标题
LincRNA Cox-2 通过调节 miR-21/NF-kappa B 轴调节脂多糖诱导的人腹膜间皮细胞炎症反应
DOI：
10.1155/2019/8626703
复制
发表时间：
2019-12-03
影响因子：
4.6
通讯作者：
Zeng, Li
中科院分区：
文献类型：
--
作者：
Bian, Yaoyao;Yang, Lili;Zeng, Li
术后腹膜粘连(PPA)是腹膜炎症过程中常见的术后并发症。本研究旨在确定大基因间非编码RNA(LincRNAs)COX-2在黏附形成的炎症反应中的生物学功能。检测COX-2在腹膜粘连组织和正常组织中的表达。用脂多糖(LPS)诱导人腹膜间皮细胞(HPMC)炎性损伤。探讨COX-2抑制对内毒素诱导的HPMCs损伤后细胞活力、细胞凋亡和炎症因子的影响。确定了COX-2和miR-21之间的调控相关性，以及miR-21的靶基因。同时，探讨了COX-2/miR-21轴对NF-kappa B通路的调节机制。提示COX-2在腹膜粘连组织中的表达高于正常组织。抑制COX-2可改善脂多糖诱导的HMPC损伤，促进细胞活力，抑制细胞凋亡和炎性因子的产生。抑制COX-2可通过负向调节miR-21逆转内毒素诱导的HPMCs损伤。MIR-21与TLR4呈负相关，TLR4被预测为miR-21的靶基因。此外，下调TLR4可逆转miR-21对脂多糖诱导的HPMCs损伤的抑制作用，从而抑制NF-kappa B途径轴的激活。提示COX-2对脂多糖诱导的HPMCs损伤的保护作用是通过负性调节miR-21和靶向TLR4途径实现的。这一发现可能为预防术后腹膜粘连提供新的视角。
Postoperative peritoneal adhesion (PPA) is a common postoperative complication caused by any peritoneal inflammatory process. This study aimed to identify the biological function of large intergenic non-coding RNAs (lincRNAs) Cox-2 in the inflammation reaction of adhesion formation. The Cox-2 expression in peritoneal adhesion tissues and normal tissues was detected. The human peritoneal mesothelium cells (HPMCs) were treated with lipopolysaccharide (LPS) to induce inflammatory injury. The effect of Cox-2 suppression on cell viability, apoptosis and inflammatory factors of LPS induced HPMCs injury were explored. The regulatory correlation between Cox-2 and miR-21, as well as the targeted genes of miR-21 were identified. Meanwhile, the regulatory mechanism of Cox-2/miR-21 axis on NF-kappa B pathway was explored. It indicated that Cox-2 was highly expressed in peritoneal adhesion tissues compared with that in normal tissues. Suppression of Cox-2 ameliorated LPS induced HMPCs injury as cell viability was promoted, and cell apoptosis and the production of inflammatory factors were inhibited. And suppression of Cox-2 reversed the LPS induced HPMCs injury by regulation of miR-21 negatively. miR-21 was negatively correlated with TLR4, and TLR4 was predicted as target gene of miR-21. Furthermore, the suppression of miR-21 on LPS induced HPMCs injury was reversed by knockdown of TLR4, which could inhibited the activation of NF-kappa B pathway axis. It suggested that the effect of Cox-2 on LPS induced HPMCs injury was achieved by negatively regulation of miR-21 and targeted TLR4 through NF-kappa B pathway axis. The findings may provide a new insight into preventing postoperative peritoneal adhesion.