Knockdown of LncRNA MALAT1 contributes to the suppression of inflammatory responses by up-regulating miR-146a in LPS-induced acute lung injury.

Abstract

BACKGROUND:

Acute lung injury (ALI) is a type of severe pulmonary inflammatory disease with high rates of morbidity and mortality. Now, an increasing number of studies suggest that lncRNAs may act as key regulators of the inflammatory response and play a crucial role in the pathogenesis of many inflammatory diseases. Our study firstly explored the function and underlying mechanism of lncRNA metastasis-associated lung adenocarcinoma transcription 1 (MALAT1) in regulating the inflammatory response of lipopolysaccharide (LPS)-induced ALI in rats.

METHODS:

The ALI rats were constructed by intratracheal instillation with LPS. Hematoxylin and eosin (HE) for histological examination were performed to detect histopathological changes in the lung tissues. Enzyme-linked immunosorbent assay (ELISA) was used to determine the concentrations of cytokines TNF-α, IL-6, and IL-1β in the supernatants of the bronchoalveolar lavage fluid (BALF). Quantitative real-time PCR (qRT-PCR) analysis was employed to assess the expression of MALAT1, miR-146a, TNF-α, IL-6, and IL-1β in lung tissues. Luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to detect the relationship between MALAT1 and miR-146a.

RESULTS:

The results revealed that MALAT1 knockdown played a protective role in the LPS-induced ALI rat model. In addition, knockdown of MALAT1 in vitro inhibited LPS-induced inflammatory response in murine alveolar macrophages cell line MH-S and murine alveolar epithelial cell line MLE-12. This study found that MALAT1 acts as a molecular sponge for miR-146a and MALAT1 negatively regulated miR-146a expression. Mechanistically, MALAT1 overexpression alleviated the inhibitory effect of miR-146a on LPS-induced inflammatory response in MH-S.

CONCLUSIONS:

Together, our study provided the first evidence that MALAT1 knockdown could suppress inflammatory response by up-regulating miR-146a in LPS-induced ALI, which provided a potential therapeutic target for the treatment of ALI.

• Authors: Lingling Dai, Guojun Zhang, Zhe Cheng, Xi Wang, Liuqun Jia, Xiaogang Jing, Huan Wang, Rui Zhang, Meng Liu, Tianci Jiang, Yuanjian Yang, Meng Yang
• Journal: Connective tissue research (Connect Tissue Res) Vol. 59 Issue 6 Pg. 581-592 (11 2018) ISSN: 1607-8438 [Electronic] England
• PMID: 29649906 (Publication Type: Journal Article)

Chemical References

• Lipopolysaccharides
• MALAT1 long noncoding RNA, rat
• MIRN146a microRNA, rat
• MicroRNAs
• RNA, Long Noncoding

Topics

• Acute Lung Injury (chemically induced, genetics, metabolism, pathology)
• Animals
• Gene Knockdown Techniques
• Inflammation (chemically induced, genetics, metabolism, pathology)
• Lipopolysaccharides (toxicity)
• MicroRNAs (biosynthesis, genetics)
• RNA, Long Noncoding (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Up-Regulation (drug effects)