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.