Abstract: FR-PO188
Long Noncoding RNA GSTM3P1/gstm2-ps1 Mediates Sepsis-Associated AKI
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
- Huang, Jing, Augusta University Department of Cellular Biology and Anatomy, Augusta, Georgia, United States
- Dong, Zheng, Augusta University Department of Cellular Biology and Anatomy, Augusta, Georgia, United States
- Wei, Qingqing, Augusta University Department of Cellular Biology and Anatomy, Augusta, Georgia, United States
Background
Long non-coding RNAs (lncRNAs) are important regulators in various kidney injuries. Our previous study has identified a pro-injurious lncRNA, GSTM3P1 (human orthologue)/gstm2-ps1 (mouse orthologue) in ischemic acute kidney injury (AKI). However, its role in other AKI conditions is unclear.
Methods
More recently, we examined the role of GSTM3P1/gstm2-ps1 in cultured renal proximal tubular cells and in mice with/without proximal tubular specific gstm2-ps1 knockout.
Results
We found that this lncRNA exacerbated sepsis-induced AKI. Overexpression of GSTM3P1 significantly increased the renal proximal tubular cell death induced by LPS treatment, evidenced by the lower cell viability by MTT assay. GSTM3P1 is a lncRNA derived from pseudogene of glutathione S-transferase Mu 3 (GSTM3), which is a protein belonging to GST family and responsible for oxidative stress detoxification by GSH conjugation. We found that GSTM3P1 regulated its parent gene GSTM3 expression, by reducing GSTM3 protein and mRNA level. A lower GSH:GSSG ratio was detected in GSTM3P1 overexpressed cells. Furthermore, the proximal tubular specific gstm2-ps1 knockout mice were protected from LPS induced AKI, showing better renal function and less tubular apoptosis in kidney.
Conclusion
In conclusion, lncRNA GSTM3P1/gstm2-ps1 contributes to renal proximal tubular cell death in sepsis AKI, potentially through the regulation of GSTM3 and enhancement of oxidative stress relief and detoxification.
Funding
- NIDDK Support