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Abstract: SA-PO163

Quantitative Proteomics Analysis of Differentially Expressed Proteins in Septic Mice Kidney With Humanin Treatment

Session Information

  • AKI: Mechanisms - III
    November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Li, Zhilian, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
  • Xiao, Zhenmeng, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
  • Shi, Qingying, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
  • Cai, Wenjing, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
  • Chen, Yuanhan, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
  • Ye, Zhiming, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
  • Liang, Xinling, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
Background

Sepsis-associated acute kidney injury (SA-AKI), which carries a high morbidity and mortality in patients, has no effective therapeutic strategies and its mechanisms are not fully understood. Increasing evidence have already showed that renal mitochondrial dysfunction plays a pivotal role in sepsis. We aimed to determine the effects of humanin, a mitochondrial-derived cytoprotective peptide on kidney injury in septic mice, and look for differentially expressed proteins after humanin treatment.

Methods

A murine model (C57BL/6 mice, 8-10 weeks, male, n=6 for each group) was constructed by one single dose of intraperitoneally lipopolysaccharide (LPS) injection (10mg/kg, LPS group) or PBS (Control group). HNG (a potent analog of humanin) was intraperitoneally injected 15 minutes later with a dose of 1mg/kg (HN group). Blood urea nitrogen (BUN), serum creatinine (Scr) and Kim-1 was determined, kidney histology staining, renal inflammatory cytokines, mitochondrial function were evaluated. To analyze the global proteome of the kidney tissue, the 4D-Label-free quantification analysis was applied to screen differentially expressed proteins in 3 groups (n=3 for each group). The parallel reaction monitoring (PRM) was used to verify the selected target proteins.

Results

HNG significantly reduced serum levels of Scr and BUN in a dose-dependent manner (0.2mg/kg, 0.4mg/kg and 1mg/kg), inhibited renal expression of IL-6, IL-1β and HMGB1 and reduce the damage of mitochondria in renal tubular epithelial cells in LPS-induced AKI. Collectively, 5900 proteins were identified in the label free quantification mass spectrometry, 5111 of which were quantifiable. NF-kappa B, Toll-like receptor, NOD-like receptor or IL-17 signaling pathways were significantly enriched,among which 7 proteins were selected for verification by PRM, and they were CD14, Casp3, Rela, Gbp2, Gbp3, Gbp5 and S100a9.

Conclusion

Humanin improves mitochondrial function and alleviates renal tubular injury in LPS-induced AKI. The map of the global proteomics enables further understanding of SA-AKI and will provide great help for seeking more potential therapeutic targets for SA-AKI.

Funding

  • Government Support – Non-U.S.