Mechanism of long non-coding RNA MALAT1 in lipopolysaccharide-induced acute kidney injury is mediated by the miR-146a/NF-κB signaling pathway

Ding,Ying; Guo,Feng; Zhu,Tao; Li,Jun; Gu,Danyan; Jiang,Weiliang; Lu,Yuying; Zhou,Daoyang

doi:10.3892/ijmm.2017.3232

Mechanism of long non-coding RNA MALAT1 in lipopolysaccharide-induced acute kidney injury is mediated by the miR-146a/NF-κB signaling pathway

Authors:
- Ying Ding
- Feng Guo
- Tao Zhu
- Jun Li
- Danyan Gu
- Weiliang Jiang
- Yuying Lu
- Daoyang Zhou
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Affiliations: Department of Intensive Care Unit, Sir Run Run Shaw Hospital Xiasha Campus, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310018, P.R. China, Department of Intensive Care Unit, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China
Published online on: November 2, 2017 https://doi.org/10.3892/ijmm.2017.3232
Pages: 446-454

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Abstract

The present study aimed to examine the expression and function of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA (miR)-146a/nuclear factor (NF)-κB axis in lipopolysaccharide (LPS)-induced acute kidney injury (AKI). The mRNA levels of MALAT1 and miR-146a in AKI tissues and cells were detected using reverse transcription-quantitative polymerase chain reaction analysis. The NF-κB pathway proteins and cell viability were assessed using western blot analysis and the MTT method, respectively. The secretion of inflammatory factors was determined using the ELISA method. The present study also examined effects of the abnormal expression of MALAT1 and miR-146a on cytokines and the NF-κB pathway. A potential binding region between MALAT1 and miR-146a was confirmed via RNA immunoprecipitation. The results revealed that the upregulation of MALAT1 reduced the expression of miR‑146a, and there was a negative linear correlation between MALAT1 and miR-146a in a RNA-induced silencing complex‑dependent manner. The expression levels of miR-146a were lower in the kidney injury specimens and NRK-52E cells, compared with those in the controls. MALAT1 knockdown and the overexpression of miR-146a reduced the production of phosphorylated inhibitor of NF-κB and np65 protein. miR‑146a was found to be transcriptionally induced by NF-κB, and miR-146a repressed the pro-inflammatory NF-κB pathway and downstream transcription factors. Taken together, these data indicated that the MALAT1/miR‑146a/NF-κB pathway exerted key functions in LPS-induced AKI, and provided novel insights into the mechanisms of this therapeutic candidate for the treatment of the disease.

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