肠道菌群代谢产物氧化三甲胺对肾小球系膜细胞和肾小管上皮细胞NF-κB/MAPK信号通路的影响
Effects of intestinal flora metabolite trimethylamine oxide on glomerular mesangial cells and renal tubular epithelial cells via NF-κB/MAPK signaling pathway
宋月娟 1杨波 1冯强生 1哈小琴1
作者信息
- 1. 联勤保障部队第九四○医院检验科,甘肃兰州 730050
- 折叠
摘要
目的 探讨肠道菌群代谢产物氧化三甲胺(trimethylamine oxide,TMAO)对人肾小球系膜细胞HMC和肾小管上皮细胞 HK-2 核因子-κB(nuclear factor-kappa B,NF-κB)/丝裂原活化蛋白激酶(mitogen activated protein kinase,MAPK)信号通路的影响,为通过肠道菌群治疗和预防肾损伤提供理论依据.方法 用TMAO处理HMC和HK-2细胞,并设未处理或TMAO处理0h对照组,Real-time PCR法检测炎性反应因子MCP-1、IL-6、TNF-α和IL-1β基因mRNA的转录水平,Western blot法检测NF-κB和MAPK信号通路相关蛋白的表达.并用NF-κB抑制剂BAY 11-7082处理HMC和HK-2细胞,验证TMAO的促炎作用.结果 与对照组相比,HMC和HK-2细胞TMAO处理组炎性反应因子MCP-1、IL-6、TNF-α和IL-1β mRNA转录水平均明显上升(t=33.349,P=0.001),TMAO对两种细胞有明显的促炎作用;TMAO可激活HMC和HK-2细胞的NF-κB及MAPK信号通路,引起炎性反应,造成对肾脏的损伤.结论 TMAO含量的增高可激活HMC和HK-2细胞NF-κB/MAPK信号通路,刺激两种细胞释放炎性反应因子,从而导致肾损伤的发生和发展.
Abstract
Objective To investigate the effects of trimethylamine oxide(TMAO),a metabolite of intestinal flora,on the nuclear factor-kappa B(NF-κB)/mitogen activated protein kinase(MAPK)signaling pathway in human glomerular mesan-gial cells HMC and renal tubular epithelial cells HK-2.Methods HMC and HK-2 cells were treated with TMAO and the control group was treated with TMAO for 0 h.The mRNA transcription levels of MCP-1,IL-6,TNF-α and IL-1β were detected by Real-time PCR,while the expression of NF-κB and MAPK signaling pathway-related proteins by Western blot.HMC and HK-2 cells were treated with NF-κB inhibitor BAY 11-7082 to verify the pro-inflammatory effects of TMAO.Results Compared with the control group,the expression levels of inflammatory factors MCP-1,IL-6,TNF-α and IL-1βmRNA significantly increased in the TMAO-treated group(t=33.349,P=0.001),indicating that TMAO had a significant pro-inflammatory effect on glomerular mesangial cells and renal tubular epithelial cells.TMAO activated NF-κB and MAPK signaling pathway in HMC and HK-2 cells,causing inflammatory response and damage to the kidney.Conclusion The increase of TMAO level can activate the NF-κB/MAPK signaling pathway in HMC and HK-2 cells,stimulate the release of inflammatory cytokines from the both kinds of cells,which leads to the occurrence and development of renal injury.
关键词
氧化三甲胺/肾损伤/信号通路/人肾小球系膜细胞/人肾小管上皮细胞Key words
Trimethylamine oxide(TMAO)/Renal injury/Signaling pathway/Human glomerular mesangial cells/Human renal tubular epithelial cells引用本文复制引用
基金项目
甘肃省自然科学基金(21JR11RA010)
联勤保障部队第九四○医院院内课题资助项目(2021yxky056)
出版年
2024
NETL
NSTL
万方数据