Abstract
Acute kidney injury (AKI) is a common and serious complication of sepsis accompanied by kidney dysfunction resulting from various etiologies and pathophysiological processes. Unfortunately, there is currently no ideal therapeutic strategy for AKI. Numerous studies have confirmed that long noncoding RNAs (lncRNAs) play important regulatory roles in the pathogenesis of sepsis-associated AKI. In this study, lncRNA TCONS_00016406 (termed lncRNA 6406), a novel lncRNA identified by using TargetScan, was significantly downregulated in the kidney tissues of mice with sepsis-associated AKI. This study aimed to explore the role of lncRNA 6406 in lipopolysaccharide (LPS)-induced AKI and its potential molecular mechanism. The models of sepsis-induced AKI (called LPS-induced AKI models) in mice and cell lines were established with male C57BL/6 mice and renal tubular epithelial (PTEC) cells, respectively. Twenty-four hours after LPS administration, kidneys and cell samples were collected after various treatments to examine the alterations in the lncRNA 6406 levels and to evaluate the effects on LPS-induced inflammation, oxidative stress, and apoptosis through real-time PCR (RT-PCR) analysis, western blotting, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The results revealed that lncRNA 6406 could significantly attenuate LPS-induced AKI, as shown by the alleviation of inflammation, the suppression of oxidative stress and the inhibition of apoptosis. Mechanistically, a luciferase reporter assay and additional research showed that lncRNA 6406 functioned as a ceRNA to sponge miRNA-687, thereby modulating LPS-stimulated AKI by targeting the miR-687/PTEN axis; thus, this study presents a novel therapeutic strategy or sepsis-associated AKI.
Highlights
Sepsis is a kind of systemic inflammatory response syndrome caused by an infection (Girardot et al, 2019; Jiang et al, 2019b; Lin et al, 2019)
To provide more evidence supporting the successful establishment of the LPS-induced Acute kidney injury (AKI) model, the level of LPS-induced cell apoptosis was examined by transferase-mediated dUTP nick end labeling (TUNEL) assay, and the TUNEL staining results showed that the number of apoptotic cells was clearly increased in the kidneys of the LPS-challenged mice (Figure 1E)
The ratio of the Bax/Bcl-2 expression level was elevated to a certain extent. These results suggested that the successful establishment of the LPS-induced AKI model presented evidence of increased inflammatory responses, oxidative stress, and apoptosis in the kidney tissues of these mice
Summary
Sepsis is a kind of systemic inflammatory response syndrome caused by an infection (Girardot et al, 2019; Jiang et al, 2019b; Lin et al, 2019). The morbidity of septic AKI caused by endotoxemia is only 3–5% in general patients, but reaches nearly 50% in LncRNA 6406 Alleviates Sepsis-Induced AKI patients in intensive care units (ICUs; Shi et al, 2019; Wiersema et al, 2019). It has been confirmed by some studies that the pathogenesis of sepsis-induced AKI is highly associated with renal hemodynamic abnormalities and inflammatory responses (Wiersema et al, 2019).
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