Effects of intestinal flora metabolite trimethylamine oxide on glomerular mesangial cells and renal tubular epithelial cells via NF-κB/MAPK signaling pathway
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.
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