Kidney Week

Abstract: SA-PO103

Secretory Leukocyte Protease Inhibitor as an Early Protective Protein and Potential Biomarker in Ischemia-Reperfusion-Induced AKI

Session Information

• AKI: Inflammation and Cell Cycle
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Chen, Fei, Affiliated Hospital of Nantong University, Nantong, Nantong , China

Fei Chen

• Wu, Yuanyuan, Nantong University School of Medicine, Nantong, Jiangsu, China

Yuanyuan Wu

• Yang, Bin, Affiliated Hospital of Nantong University, Nantong, China

Bin Yang, MD, PhD

Background

Ischemia reperfusion (IR) injury is one of main causes of acute kidney injury (AKI) that is a common syndrome characterized by a sudden decline of renal function and lacking early diagnosis and effective intervention. Secretory leukocyte protease inhibitor (SLPI) is an acute response protein that is associated with IR-induced AKI and repair, but its dynamic change, exact roles and underlying mechanisms remain unknown.

Methods

C57BL/6 mice was used to establish a time-course model of IR-AKI. Bilateral kidney pedicles were clamped for 30 minutes (min) followed by reperfusion for 6 hours (h) to 4 weeks (w), the expression and localization of SLPI were monitored. In vitro, a mouse kidney epithelial cell line TCMK-1 was treated with hydrogen peroxide (H₂O₂) to mimic IR injury. The effects of erythropoietin-derived helix B surface peptide (HBSP) or targeted siRNA on SLPI expression were further observed. The downstream cellular apoptosis and injury markers, as well as the phagocytic ability of TCMK-1 cells through uptaking fluorescent-labeled E. Coli were then assessed.

Results

The increase of serum SLPI in IR group mice was at 12 h earlier than that of serum creatinine. The renal expression of SLPI was also up-regulated as early as 12 h post IR injury, as well as in TCMK-1 cells, prior to the changes of inflammation and apoptosis related indicators. SLPI was mainly located in tubular epithelial cells of IR kidney. HBSP significantly increased SLPI expression in a dose-dependent manner. Moreover, SLPI siRNA further increased cellular apoptosis, cleaved-caspase3, HMGB1, IL-6 and TNF-α in TCMK-1 cells treated with H₂O₂, but inhibited the phagocytosis of TCMK-1 cells.

Conclusion

SLPI was increased early upon IR-induced kidney injury, acting as a protective factor to regulate apoptosis, inflammation and phagocytosis. The up-regulation of SLPI may be one of the mechanisms that HBSP protects IR-AKI. In summary, SLPI not only serves as a potential biomarker, but also a protector against AKI.