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Inhibition of MicroRNA-214 Alleviates Lung Injury and Inflammation via Increasing FGFR1 Expression in Ventilator-Induced Lung Injury
- Source :
- Lung. February, 2021, Vol. 199 Issue 1, p63, 10 p.
- Publication Year :
- 2021
-
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.<br />Author(s): Kun He [sup.1], Shuang Han [sup.2], Li An [sup.1], Jin Zhang [sup.1] Author Affiliations: (1) Department of Anesthesiology, The Fourth Hospital of Shijiazhuang, , No. 206, Zhongshan East Road, [...]
Details
- Language :
- English
- ISSN :
- 03412040
- Volume :
- 199
- Issue :
- 1
- Database :
- Gale General OneFile
- Journal :
- Lung
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.651234316
- Full Text :
- https://doi.org/10.1007/s00408-020-00415-5