Abstract
Background
Sepsis is an organ dysfunction caused by the dysregulated inflammatory response to infection. LBP binds to LPS, and modulates the inflammatory response. Rare systematic study has been reported to detect the effect of LBP gene during the LPS-induced sepsis. Herein, we explored the RNA sequencing technology to profile the transcriptomic changes in liver tissue between LBP-deficient rats and WT rats at multiple timepoints after LPS administration.
Results
We compared the serum ALT levels using the biochemistry analyzer and proceeded RNA sequencing of liver tissue to search differentially expressed genes and enriched biological processes and pathways between LBP-deficient and WT groups at 0 h, 6 h, and 24 h. In total, 168, 284, and 307 differential expressed genes (DEGs) were identified at 0 h, 6 h, and 24 h respectively, including Lrp5, Cyp7a1, Nfkbiz, Sigmar1, Fabp7, and Hao1, which are related to the inflammatory or lipid-related process. Functional enrichment analysis revealed that inflammatory response to LPS mediated by Ifng, Cxcl10, Serpine1, and Lbp was enhanced at 6 h, while lipid-related metabolism associated with C5, Cyp4a1, and Eci1 was enriched at 24 h after LPS administration in the WT samples. The inflammatory process was not found when the LBP gene was knocked out, lipid-related metabolic process and PPAR signaling pathway mediated by Dhrs7b and Tysnd1 were significantly activated in LBP-deficient samples.
Conclusions
Our study suggested that the invading LPS may interplay with LBP to activate NF-κB signaling pathway and trigger uncontrolled inflammatory response. However, when inhibiting the activity of NF-κB, lipid-related metabolism would make bacteria removal via the effect on PPAR signaling pathway in the absence of LBP gene. Moreover, we further found the potent implications of targeting the LBP gene may as a biomarker for inflammatory conditions induced by metabolic disorders.