The lncRNA CASC9 alleviates lipopolysaccharide-induced acute kidney injury by regulating the miR-424-5p/TXNIP pathway
Hai-Peng Fan1, Zhi-Xia Zhu1, Jia-Jun Xu1
1Department of Emergency, First Hospital of Quanzhou affiliated to Fujian Medical University, Fujian, Quanzhou, China.
Objective:
This study aimed to clarify the mechanism by which the long non-coding RNA cancer susceptibility candidate 9 (CASC9) alleviates sepsis-related acute kidney injury (S-AKI).
Methods:
A lipopolysaccharide (LPS)-induced AKI model was established to simulate S-AKI. HK-2 human renal tubular epithelial cells were treated with LPS to establish an in vitro model, and mice were intraperitoneally injected with LPS to generate an in vivo model. Subsequently, the mRNA expression of inflammatory and antioxidant factors was validated by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Reactive oxygen species (ROS) production was assessed using an assay kit. Apoptosis was detected by western blotting and fluorescence-activated cell sorting.
Results:
CASC9 was significantly downregulated in the LPS-induced AKI model. CASC9 attenuated cell inflammation and apoptosis and enhanced the antioxidant capacity of cells. Regarding the mechanism, miR-424-5p was identified as the downstream target of CASC9, and the interaction between CASC9 and miR-424-5p promoted thioredoxin-interacting protein (TXNIP) expression.
Conclusions:
CASC9 alleviates LPS-induced AKI in vivo and in vitro, and CASC9 directly targets miR-424-5p and further promotes the expression of TXNIP. We have provided a possible reference strategy for the treatment of S-AKI.
Insights
The long non-coding RNA CASC9 alleviates sepsis-related acute kidney injury by targeting miR-424-5p and promoting TXNIP expression. This study offers a potential therapeutic strategy for acute kidney injury.
Area of Science:
- Molecular Biology
- Renal Physiology
- Biochemistry
Background:
- Sepsis-related acute kidney injury (S-AKI) is a critical condition with limited treatment options.
- The role of long non-coding RNAs (lncRNAs) in S-AKI pathogenesis is an emerging area of research.
Purpose of the Study:
- To elucidate the mechanism by which lncRNA CASC9 mitigates S-AKI.
- To investigate the regulatory pathway involving CASC9, miR-424-5p, and TXNIP in S-AKI.
Main Methods:
- Established lipopolysaccharide (LPS)-induced in vitro (HK-2 cells) and in vivo (mice) models of S-AKI.
- Quantified mRNA expression of inflammatory and antioxidant factors using RT-qPCR.
- Assessed reactive oxygen species (ROS) production and apoptosis via specific assay kits, western blotting, and fluorescence-activated cell sorting.
Main Results:
- CASC9 expression was significantly downregulated in LPS-induced AKI models.
- CASC9 overexpression attenuated inflammation and apoptosis while enhancing antioxidant capacity in renal cells.
- miR-424-5p was identified as a direct downstream target of CASC9, and their interaction promoted TXNIP expression.
Conclusions:
- CASC9 exerts protective effects against LPS-induced AKI both in vitro and in vivo.
- CASC9 directly targets miR-424-5p, leading to the promotion of TXNIP expression.
- This CASC9/miR-424-5p/TXNIP axis presents a potential therapeutic target for S-AKI treatment.
