miR‑21‑5p ameliorates hyperoxic acute lung injury and decreases apoptosis of AEC II cells via PTEN/AKT signaling in rats

Qin,Song; Wang,Hongliang; Liu,Guoyue; Mei,Hong; Chen,Miao

doi:10.3892/mmr.2019.10779

miR‑21‑5p ameliorates hyperoxic acute lung injury and decreases apoptosis of AEC II cells via PTEN/AKT signaling in rats

Authors:
- Song Qin
- Hongliang Wang
- Guoyue Liu
- Hong Mei
- Miao Chen
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Affiliations: Intensive Care Unit, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
Published online on: October 30, 2019 https://doi.org/10.3892/mmr.2019.10779
Pages: 4953-4962
Copyright: © Qin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Inhibiting apoptosis of type II alveolar epithelial cells (AEC II) is an effective way to decrease hyperoxic acute lung injury (HALI); however, the specific underlying molecular mechanisms have not yet been fully elucidated. Although miRNA‑21‑5p has previously been reported to decrease H2O2‑induced AEC II apoptosis by targeting PTEN in vitro, whether miR‑21‑5p can decrease HALI in vivo and the downstream molecular mechanisms remain unclear. In the present study, rats were endotracheally administered with an miR‑21‑5p‑encoding (AAV‑6‑miR‑21‑5p) or a negative control adenovirus vector, and then a HALI model was established by exposure to hyperoxia. At 3 weeks following the administration of AAV‑6‑miR‑21‑5p, the severity of HALI was decreased, as evidenced by the improved outcome of the oxygenation index, respiratory index, wet/dry weight ratio and pathological scores of the HALI lungs. To further investigate the underlying mechanisms, AEC II cells were isolated from the lungs of the experimental rats and cultured. The expression levels of miR‑21‑5p and its target gene, PTEN, were detected, as well as the levels of phosphorylated and total AKT. In addition, the apoptosis rate of AEC II was detected by flow cytometry. The results demonstrated that AAV‑6‑miR‑21‑5p administration increased the miR‑21‑5p levels in primary AEC II cells, while it decreased the expression levels of PTEN. miR‑21‑5p overexpression also increased AKT phosphorylation in AEC II cells from the HALI lungs compared with that of the HALI alone group and the control virus group. The present study indicated that miR‑21‑5p ameliorated HALI in vivo, which may have resulted from the inhibition of PTEN/AKT‑induced apoptosis of AEC II cells. These findings suggest that miR‑21‑5p and PTEN/AKT signaling might serve as potential targets for HALI treatment.

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