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Abstract: FR-PO136

Helix B Surface Peptide Protects Lipopolysaccharide-Induced AKI by Inhibiting Pyroptosis and Promoting Macrophage Polarization

Session Information

  • AKI: Mechanisms - II
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Huang, Lili, Affiliated Hospital of Nantong University, Nantong, China
  • Sai, Wenli, Affiliated Hospital of Nantong University, Nantong, China
  • Xiong, Fenfen, Affiliated Hospital of Nantong University, Nantong, China
  • Feng, Guijuan, Affiliated Hospital of Nantong University, Nantong, China
  • Wu, Yuanyuan, Nantong University, Nantong, China
  • Zhao, Hongsheng, Affiliated Hospital of Nantong University, Nantong, China
  • Yang, Bin, Affiliated Hospital of Nantong University, Nantong, China
Background

Sepsis is defined as life-threatening multiple organ dysfunction syndrome caused by a dysregulated host response to infection. Acute kidney injury (AKI) is one of the most common complications of sepsis. Helix B surface peptide (HBSP) is the derivative of erythropoietin (EPO) that retains the tissue protection of EPO, without erythropoiesis. Previous studies have shown that HBSP alleviated renal ischemia-reperfusion injury. In this study, we investigated the effect of HBSP on pyroptosis and underlying mechanisms in lipopolysaccharide (LPS)-induced AKI.

Methods

The mice were randomly divided into three groups:the control,LPS and LPS + HBSP group (n = 6-8). Serum creatinine (SCr) and blood urea nitrogen (BUN) were detected by the Fully Automatic Biochemical Analyzer, while tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-18 and IL-1β were detected by quantitative real-time PCR (qPCR). Renal histological changes were evaluated by tubular interstitial damage (TID) score in H&E stained sections. Macrophage infiltration and polarization were analyzed by immunohistochemistry and flow cytometry measures. The expression of pyroptosis-related proteins was detected by Western Blot.

Results

SCr, BUN and TID score were increased by LPS compared with the control group, but was decreased by HBSP (P<0.01). The level of TNF-α, IL-6, IL-18 and IL-1β mRNA, as well as HMGB1 protein, was increased by LPS, but reduced again by HBSP (P<0.05). In addition, the pyroptosis in LPS-treated kidneys was obvious compared with the control group, but HBSP treatment reduced the expression of pyroptosis-related proteins including GSDMD-N and IL-1β and IL-18 (P<0.05). Macrophage infiltration and inflammation in the kidney were increased by LPS, but reduced by HBSP (P<0.05). Moreover, M1 macrophage activation was induced by LPS, while the transformation of M1 to M2 phenotype was promoted by HBSP (P<0.01).

Conclusion

The model of LPS-induced AKI was successfully established with increased inflammatory mediators and compromised renal function and histology. HBSP effectively protected LPS-induced AKI reflected by less inflammation and pryoptosis, and improved macrophage polarization, renal function and structure. These findings provide new insights to the therapeutic strategy of LPS-induced AKI.