The lncRNA CASC9 alleviates lipopolysaccharide-induced acute kidney injury by regulating the miR-424-5p/TXNIP pathway.

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). 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. 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. 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.

Citation

Hai-Peng Fan, Zhi-Xia Zhu, Jia-Jun Xu, Yu-Tang Li, Chun-Wen Guo, Hong Yan. The lncRNA CASC9 alleviates lipopolysaccharide-induced acute kidney injury by regulating the miR-424-5p/TXNIP pathway. The Journal of international medical research. 2021 Aug;49(8):3000605211037495

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PMID: 34407684

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