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Published in: Lung 1/2021

01-02-2021 | Ponatinib | VENTILATOR-INDUCED LUNG INJURY

Inhibition of MicroRNA-214 Alleviates Lung Injury and Inflammation via Increasing FGFR1 Expression in Ventilator-Induced Lung Injury

Authors: Kun He, Shuang Han, Li An, Jin Zhang

Published in: Lung | Issue 1/2021

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Abstract

Purpose

Ventilator-induced lung injury (VILI) is an additional inflammatory injury caused by mechanical ventilation (MV). This study aimed to determine the effects of microRNA-214 (miR-214) on VILI and its underlying mechanism of action.

Methods

To develop a VILI mouse model, mice were subjected to MV. The expression of miR-214 was detected by qRT-PCR. The macrophages, fibroblasts, epithelial cells, and endothelial cells were isolated from lung tissues by fluorescence-activated cell sorting. The histopathological changes of lung, lung wet/dry weight (W/D) ratio, and myeloperoxidase (MPO) activity were used to evaluate the degree of lung injury. The levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter assay was performed to determine the interactions between miR-214 and FGFR1. Western blot was used to detect the protein expression of FGFR1, p-AKT, and p-PI3K.

Results

The expression of miR-214 was increased in lung tissues and macrophages, fibroblasts, epithelial cells, and endothelial cells isolated from lung tissues in VILI mice. MiR-214 inhibition decreased the histopathological changes of lung, lung W/D ratio, MPO activity, and pro-inflammatory cytokines levels in BALF in VILI mice. FGFR1 was targeted by miR-214. The protein expression of FGFR1 was decreased in VILI mice. Ponatinib (FGFR1 inhibitor) reversed the suppressive effects of miR-214 inhibition on lung injury and inflammation of VILI mice. MiR-214 increased the activity of PI3K/AKT pathway by regulating FGFR1.

Conclusions

Inhibition of miR-214 attenuated lung injury and inflammation in VILI mice by increasing FGFR1 expression, providing a novel therapeutic target for VILI.
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Metadata
Title
Inhibition of MicroRNA-214 Alleviates Lung Injury and Inflammation via Increasing FGFR1 Expression in Ventilator-Induced Lung Injury
Authors
Kun He
Shuang Han
Li An
Jin Zhang
Publication date
01-02-2021
Publisher
Springer US
Keyword
Ponatinib
Published in
Lung / Issue 1/2021
Print ISSN: 0341-2040
Electronic ISSN: 1432-1750
DOI
https://doi.org/10.1007/s00408-020-00415-5

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