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A novel miRNA-762/NFIX pathway modulates LPS-induced acute lung injury.

Authors :
Zhang XL
An J
Deng YZ
Fang XZ
Xu CY
Liu XF
Bai ZH
Zhang G
Cui MY
Source :
International immunopharmacology [Int Immunopharmacol] 2021 Nov; Vol. 100, pp. 108066. Date of Electronic Publication: 2021 Sep 04.
Publication Year :
2021

Abstract

Severe acute lung injury (ALI) cause significant morbidity and mortality worldwide. MicroRNAs (miRNAs) are possible biomarkers and therapeutic targets for ALI. We aimed to explore the role of miR-762, a known oncogenic factor, in the pathogenesis of ALI. Levels of miR-762 in lung tissues of LPS-treated ALI mice and blood cells of patients with lung injury were measured. Injury of human lung epithelial cell line A549 was induced by LPS stimulation. A downstream target of miR-762, NFIX, was predicted using online tools. Their interactions were validated by luciferase reporter assay. Effects of targeted regulation of the miR-762/NFIX axis on cell proliferation, apoptosis, and inflammatory responses were tested in vitro in A549 cells in vivo with an ALI mouse model. We found that upregulation of miR-762 expression and downregulation of NFIX expression were associated with lung injury. Either miR-762 inhibition or NFIX overexpression in A549 lung cells significantly attenuated LPS-mediated impairment of cell proliferation and viability. Notably, increasing expressions of miR-762 inhibitor or NFIX in vivo via airway lentivirus infection alleviated the LPS-induced ALI in mice. Further, targeted downregulation of miR-762 expression or upregulation of NFIX expression in A549 cells markedly down-regulates NF-κB/IRF3 activation, and substantially reduces the production of inflammatory factors, including TNF-α, IL-6, and IL-8. This study reveals a novel role for the miR-762/NFIX pathway in ALI pathogenesis and sheds new light on targeting this pathway for diagnosis, prevention, and therapy.<br /> (Copyright © 2021 Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1878-1705
Volume :
100
Database :
MEDLINE
Journal :
International immunopharmacology
Publication Type :
Academic Journal
Accession number :
34492536
Full Text :
https://doi.org/10.1016/j.intimp.2021.108066