No abstract

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.

Long noncoding RNAs (lncRNAs) Colorectal Neoplasia Differentially Expressed (CRNDE) and taurine-upregulated gene 1 (TUG1) play similar roles in sepsis, indicating the existence of the crosstalk between them. Sepsis is a major cause of injuries in heart, which are related to high mortality rates. This study was therefore carried out to analyze the potential crosstalk between CRNDE and TUG1 in sepsis, with a focus on sepsis-induced cell apoptosis in heart. Expression of CRNDE and TUG1 was analyzed with RT-qPCR. Correlations between them were analyzed by Pearson’s correlation coefficient. CRNDE and TUG1 were overexpressed in cardiomyocytes to determine the relationship between them. The roles of CRNDE and TUG1 in regulating the apoptosis of cardiomyocytes were explored by cell apoptosis assay. We found that both CRNDE and TUG1 were downregulated in sepsis. In cardiomyocytes, LPS treatment resulted in the downregulation of CRNDE and TUG1. Overexpression of CRNDE and TUG1 in cardiomyocytes increased the expression levels of each other. Under lipopolysaccharide (LPS) treatment, decreased apoptosis rates of cardiomyocytes were observed after CRNDE and TUG1 overexpression. CRNDE and TUG1 co-overexpression showed a stronger effect. In conclusion, CRNDE and TUG1 are downregulated in sepsis and they positively regulate each other to suppress the apoptosis of cardiomyocytes.