Upregulation of Mitochondrial Transcription Factor A Promotes the Repairment of Renal Tubular Epithelial Cells in Sepsis by Inhibiting Reactive Oxygen Species-Mediated Toll-Like Receptor 4/p38MAPK Signaling

摘要: Background Mitochondrial transcription factor A (TFAM) plays multiple pathophysiologic roles in mitochondrial DNA (mtDNA) maintenance. However, the role of TFAM sepsis-induced acute kidney injury (AKI) remains largely unknown. Methods Lipopolysaccharide (LPS) treatment HK-2 cells mimics vitro model AKI inflammation. pcDNA3.1 plasmid was used to construct pcDNA3.1-TFAM. sh-TFAM-543, sh-TFAM-717, sh-TFAM-765, sh-TFAM-904 and pcDNA3.1-TFAM were transfected into using Lipofectamine 2000. MtDNA transcriptional levels detected by quantitative real-time polymerase chain reaction (qRT-PCR). 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay performed assess cell viability. Changes reactive oxygen species (ROS) membrane potential corresponding kits. Immunofluorescence experiment investigate displacement TFAM. mRNA protein expression its related genes measured qRT-PCR western blot respectively. Mice sepsis administered cecal ligation puncture surgery. Results LPS a non-lethal influencing factor, leading upregulation ROS downregulation mtDNA copy number NADH dehydrogenase subunit-1 (ND1) expression, caused damage mitochondria. As time increased, displaced from periphery nucleus cytoplasm. reduced P38MAPK inhibiting toll-like receptor 4 (TLR4) ultimately inflammation repairing mtDNA. Conclusions Our results indicate that repairs blocking TLR4/ROS/P38MAPK signaling pathway inflammatory cells, thereby septic tubular epithelial may serve as new target for therapy.