miR-7-5p Antagomir Protects Against Inflammation-Mediated Apoptosis and Lung Injury via Targeting Raf-1 In Vitro and In Vivo.

Abstract

Exacerbated inflammation and apoptosis are considered upstream events associated with acute lung injury (ALI). microRNAs are critical regulators of genes responsible for inflammation and apoptosis and are considered potential therapeutic targets for ameliorating ALI. This study was undertaken to uncover the role of miR-7-5p in LPS-induced lung injury. A LPS-induced inflammation model was established using BEAS-2B cells and C57BL/6 mice. Bioinformatics analysis and the luciferase reporter assay confirmed that Raf-1 is a target of miR-7-5p and that its expression was inversely correlated with expression of proinflammatory markers and miR-7-5p, whereas miR-7-5p inhibition in vitro led to subsequent restoration of Raf-1 expression and prevention of apoptosis. Intranasal (i.n.) administration of antagomir using the C57BL/6 mouse model further confirmed that miR-7-5p inhibition suppresses LPS-induced inflammation and apoptosis via modulating the miR-7-5p/Raf-1 axis. Our findings indicate that blocking miR-7-5p expression by antagomir protects mice from LPS-induced lung injury by suppressing inflammation and activation of mitochondria-mediated survival signalling. In conclusion, our findings demonstrate a previously unknown pathophysiological role of miR-7-5p in the progression of ALI, and targeted i.n. administration of miR-7-5p antagomir could aid in the development of potential therapeutic strategies against lung injury.

• Authors: Divya Peethambaran, Bijesh Puthusseri, Gyanendra Kumar, Rajasekar Janani, Parvatam Giridhar, Vallikannan Baskaran
• Journal: Inflammation (Inflammation) Vol. 46 Issue 3 Pg. 941-962 (Jun 2023) ISSN: 1573-2576 [Electronic] United States
• PMID: 36701049 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Antagomirs
• Lipopolysaccharides
• MicroRNAs

Topics

• Animals
• Mice
• Antagomirs
• Lipopolysaccharides (pharmacology)
• Mice, Inbred C57BL
• Acute Lung Injury (chemically induced, prevention & control, metabolism)
• MicroRNAs (metabolism)
• Inflammation
• Apoptosis