Regulatory effect of lncRNA NKILA on autophagy induced by sepsis kidney injury

Y.-M. Yang, Y.-H. Li, L.-L. Ding, Y. Fu, N. Li

Department of Intensive Care Unit, First Hospital of Jilin University, Changchun, China. leenan79@163.com

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• Infectious Diseases

OBJECTIVE: The aim of this study was to investigate the regulatory effect of long non-coding RNA (lncRNA) NKILA on autophagy in sepsis-induced kidney injury.
MATERIALS AND METHODS: Sepsis model was successfully established in rats by cecal ligation and puncture (CLP). Hematoxylin and eosin (HE) staining was performed to evaluate the pathological lesions in rat kidney tissues. Subsequently, serum samples of sepsis rats were collected. The levels of blood urea nitrogen (BUN) and serum creatinine (SCr) were determined. Western blot and quantitative real time-polymerase chain reaction (qRT-PCR) were conducted to detect the protein and mRNA expression levels of LC3, Beclin-1, activated caspase-3, p-Akt (308), p-Akt (472), Akt and NKILA in kidney tissues of sepsis rats at different time points, respectively. Subsequently, HK-2 cells were induced with different doses of lipopolysaccharide (LPS) for different time points. The expression levels of the above genes in cells were detected as well. Finally, changes in autophagy and apoptosis in LPS-induced HK-2 cells with the treatment of PI3K pathway inhibitor or Akt inhibitor were observed.
RESULTS: Typical pathological lesions were observed in kidney tissues of sepsis rats, with increased serum levels of BUN and SCr. This indicated the successful construction of the sepsis model in rats. The expression levels of LC3, Beclin-1, and NKILA/Akt significantly increased in kidney tissues of sepsis rats. In vitro experiments revealed that NKILA expression in HK-2 cells gradually up-regulated with the increase of LPS dose and prolongation of LPS induction. The expressions of LC3 and NKILA/Akt were higher at 10 mg/L LPS treatment, and 8 h of LPS induction. Furthermore, the treatment of PI3K pathway inhibitor or Akt inhibitor remarkably down-regulated LPS-induced LC3 expression, while it accelerated cell apoptosis and up-regulated NKILA expression.
CONCLUSIONS: Autophagy occurs at sepsis-induced kidney injury, which can be regulated by NKILA/Akt pathway.

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