Abstract: SA-PO1189
Regulation of NLRP3 Inflammasome Expression through Inhibition of Podocyte-Specific Lysyl Oxidase-Like 2 as a New Therapeutic Target for AKI on CKD
Session Information
- CKD: Mechanisms - 3
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Choi, Hoon Young, Yonsei University College of Medicine, Seodaemun-gu, Korea (the Republic of)
- Jeon, Nara, Yonsei University College of Medicine, Seodaemun-gu, Korea (the Republic of)
- Lim, Beom Jin, Yonsei University College of Medicine, Seodaemun-gu, Korea (the Republic of)
Background
The NLRP3 inflammasome activation has been suggested a potential role in renal inflammation and thus contribute to the progression of kidney disease. Lysyl oxidase-like 2 (LOXL2) has been known to play an important role in target organ fibrosis including heart, liver and lung. In this study, we investigated the expression of LOXL2 in human kidney and podocyte, and its contribution to the NLRP3 inflammasome expression in the progression of acute kidney injury (AKI) on chronic kidney disease (CKD).
Methods
A podocyte cell line that suppresses LOXL2 expression was generated to investigate the role of LOXL2 in podocytes. And also, the podocyte-specific LOXL2-inhibiting mice (Nphs2-Cre:Loxl2-/-) was constructed to determine the role of LOXL2 in renal podocytes mice to determine the role of LOXL2 in renal podocytes in an animal model of AKI on CKD progression using lipopolysaccharide (LPS) and streptozotocin injection.
Results
Gene silencing of LOXL2 significantly reduced NLRP3 mRNA and protein expression in human podocytes (1.19±0.16 vs. 1.87±0.16, P<0.05). In hyperglycemic mice treated with LPS, podocyte-specific LOXL2 deficiency significantly reduced NLRP3 mRNA and protein expression in human kidney glomerulus. Western blot analysis also showed that TGF-beta 1, collagen I and phosphorylated Smad2 protein expression were significantly decreased in podocyte-specific LOXL2 deficiency mice.
Conclusion
Our results demonstrated that the genetic manipulation of podocyte-specific LOXL2 expression on NLRP3 inflammasome expression in AKI on CKD, suggesting its potential as a new therapeutic target for the mechanism of AKI on CKD.
Funding
- Government Support – Non-U.S.