Abstract: FR-PO193
Role of HTRA1 in an Ischemia-Reperfusion (I/R)-Induced AKI-Mice Model
Session Information
- AKI: Mechanisms
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Wikan, Naruemon, The University of Utah School of Medicine, Salt Lake City, Utah, United States
- Beck, Laurence H., Boston University, Boston, Massachusetts, United States
- Al-Rabadi, Laith, The University of Utah School of Medicine, Salt Lake City, Utah, United States
- Oka, Chio, Nara Sentan Kagaku Gijutsu Daigakuin Daigaku Sentan Kagaku Gijutsu Kenkyuka Bioscience Ryoiki, Ikoma, Nara, Japan
Background
Ischemia-Reperfusion (I/R), commonly observed in surgical settings, heightens risks of acute kidney injury (AKI), mainly attributed to sudden decreases in blood flow, which cause deoxygenation and increases in reactive oxygen radicals. An important member of the heat-shock-induced serine protease group, HTRA1 plays a role in extracellular matrix’s homeostasis, by cleaving numerous substrates.
Methods
As HTRA1’s role in kidney functions has yet to be elucidated, the research group opted to investigate its function in the AKI I/R setting. HTRA1-knockout (KO) and wild type (WT) mice (C57BL/6) underwent unilateral renal pedicle clamping, thereby replicating AKI I/R injury with a flank incision with 30 m occlusion time until nephrectomy and after 24 h and 72 h reperfusion.
Results
Renal tubular injury was observed in WT and KO mice, after 24 hours. However, it was prolonged and persistent in the HTRA1 KO mice, and still evident after 72 hours. This was supported by the presence of the kidney injury molecule-1 (KIM-1), an AKI marker. Regarding AKI I/R-KO there were significantly increased inflammatory cascade and oxidative stress, along with decreased levels of anti-oxidant and autophagy activation.
Conclusion
HTRA1 could play an efficacious role in kidney recovery, given the impact of AKI I/R’s role in causing renal tubular injury.
Kidney histopathological assessments (H&E stainig)
Funding
- NIDDK Support