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Title: Effect of lncRNA CRNDE on sepsis-related kidney injury through the TLR3/NF-κB pathway.
Author: Sun BQ, Sui YD, Huang H, Zou XB, Chen SC, Yu ZK.
Journal: Eur Rev Med Pharmacol Sci; 2019 Dec; 23(23):10489-10497. PubMed ID: 31841203.
Abstract:
OBJECTIVE: The aim of this study was to detect the expression of long non-coding ribonucleic acid (lncRNA) colorectal neoplasia differentially expressed gene (CRNDE) in the kidney tissues of mice with sepsis-induced acute kidney injury (AKI) and its effect on KI, and to further explore its mechanism. MATERIALS AND METHODS: A total of 60 male C57 mice were randomly divided into 3 groups based on a random number table, including the control group (Sham group, n=20), sepsis-related KI group [lipopolysaccharide (LPS) group, n=20] and CRNDE inhibition group [LPS + CRNDE small interfering ribonucleic acid (siRNA) group, n=20]. Mice in LPS and LPS + CRNDE siRNA groups were intraperitoneally injected with 5 mg/kg LPS, while the tail vein was injected with 5 μL CRNDE siRNAs. After 12 h, the expression level of lncRNA CRNDE in kidney tissues of mice in each group was detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR). At the same time, 2 mL of orbital blood was collected from each mouse, and the levels of creatinine and blood urea nitrogen were detected. Subsequently, kidney tissue samples were collected from mice in each group. Periodic acid Schiff (PAS) staining was used to assess the injury of renal tubulointerstitium, followed by scoring. Hematoxylin and eosin (H&E) staining was applied to detect cell injury in kidney tissues. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was adopted to examine the apoptosis in kidney tissues in mice of each group. Meanwhile, the distribution and expression of p65 in kidney tissues of mice in each group were determined via immunohistochemical staining. Finally, the expression of Toll-like receptor 3 (TLR3)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway in kidney tissues of mice in each group was detected using Western blotting. RESULTS: Compared with the Sham group, lncRNA CRNDE level in the kidney of the LPS group was remarkably up-regulated (p<0.05). The levels of creatinine and blood urea nitrogen in LPS + CRNDE siRNA group were notably lower than those of the LPS group (p<0.05). PAS staining results manifested that renal tubulointerstitial injury in the LPS group was significantly more serious than that of the LPS + CRNDE siRNA group (p<0.05). According to H&E staining results, serious edema, rupture and necrosis observed in kidney tissue cells of the LPS group. However, after the intervention of CRNDE siRNA, cell edema and necrosis were markedly relieved. In addition, TUNEL staining results indicated that the apoptotic level of kidney tissue cells in the LPS + CRNDE siRNA group was significantly lower than that of the LPS group (p<0.05). Subsequent immunofluorescence staining demonstrated that p65 expression in the LPS group increased significantly, which was markedly inhibited by CRNDE siRNA intervention (p<0.05). Furthermore, Western blotting displayed that CRNDE siRNA could effectively inhibit the activation of TLR3 and p65 in mouse kidney tissue induced by LPS (p<0.05). CONCLUSIONS: Inhibition of CRNDE can reduce sepsis-induced KI by blocking the activation of the TLR3/NF-κB pathway. Moreover, CRNDE is expected to become a target for clinical treatment of sepsis-related KI.

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