Abstract: TH-PO114
Inhibition of Semaphorin-3a Suppresses Lipopolysaccharide-Induced AKI
Session Information
- AKI: Inflammation, New Technologies, Omics
October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Tian, Xiaofang, The First Affiliated hospital of Chongqing Medical University, Chongqing, China
- Gan, Hua, The First Affiliated hospital of Chongqing Medical University, Chongqing, China
- Zeng, Yizhou, The First Affiliated hospital of Chongqing Medical University, Chongqing, China
- Zhao, Hongfei, The First Affiliated hospital of Chongqing Medical University, Chongqing, China
- Tang, Rong, The First Affiliated hospital of Chongqing Medical University, Chongqing, China
- Xia, Yunfeng, The First Affiliated hospital of Chongqing Medical University, Chongqing, China
Background
Acute kidney injury (AKI) is a common and catastrophic complication in sepsis-associated patients. Endotoxin is a common cause of sepsis-associated AKI. Lipopolysaccharide (LPS) is the major component of endotoxin derived from gram-negative bacteria and has been found to be involved in the pathogenesis of AKI. Semaphorin-3a (Sema3A), a soluble axon guidance cue, appears to play an important role in the development of AKI. However, the role of Sema3A in sepsis related AKI remains unknown.
Methods
Lipopolysaccharide (LPS) was used to simulate sepsis-associated AKI in male C57BL/6 mice and NRK-52E cells (rat tubular epithelial cells). The role of Sema3A in LPS-induced AKI was investigated in vivo and in vitro. Firstly, mice were intraperitoneally injected by LPS with different times to examine Sema3A expression. Next, (-)-Epigallocatechin-3-gallate (EGCG) was administrated to inhibit Sema3A. Then, Renal function, kidney injury, inflammation, and apoptosis were measured to investigate the effect of Sema3A in LPS-induced AKI. Furthermore, to explore the mechanism of Sema3A regulates inflammation and apoptosis in vitro, NSC23766 (a specific Rac1 inhibitor) and SP600125 (a specific JNK inhibitor) were used. Then, the mRNA expression of IL-6 and TNF-α, cell apoptosis, the expression of Rac1/NF-κBp65 and JNK signaling molecules were examined.
Results
The expression of Sema3A was upregulated in renal tubular epithelial cells (TECs) in LPS induced AKI model. Similar change was found in NRK-52E cells incubated with LPS (5μg/ml). Notably, inhibition of Sema3A by EGCG significantly reduced renal inflammation and the apoptosis of TECs in LPS induced AKI mice. EGCG intervention also ameliorated LPS-induced inflammation and apoptosis in NRK-52E cells in vitro. Our results also indicated that Rac1/NF-κBp65 and JNK signaling were involved in Sema3A-mediated inflammation and apoptosis of TECs, respectively.
Conclusion
Our results suggested that the upregulation of Sema3A probably play a pathogenic role in LPS-induced AKI, which promote renal inflammation and TECs apoptosis. Rac1/NF-κBp65 and JNK signaling pathways might be involved in the inflammation and cell apoptosis respectively.