MicroRNA‑93 contributes to the suppression of lung inflammatory responses in LPS‑induced acute lung injury in mice via the TLR4/MyD88/NF‑κB signaling pathway

Gao,Hu; Xiao,Dongqiong; Gao,Linbo; Li,Xihong

doi:10.3892/ijmm.2020.4610

MicroRNA‑93 contributes to the suppression of lung inflammatory responses in LPS‑induced acute lung injury in mice via the TLR4/MyD88/NF‑κB signaling pathway

Authors:
- Hu Gao
- Dongqiong Xiao
- Linbo Gao
- Xihong Li
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Affiliations: Department of Emergency, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610000, P.R. China, Laboratory of Molecular Translational Medicine, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610000, P.R. China
Published online on: May 19, 2020 https://doi.org/10.3892/ijmm.2020.4610
Pages: 561-570
Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute lung injury (ALI) is a severe inflammatory lung disease with a rapid onset. The anti‑inflammatory functions of microRNA‑93 (miRNA/miR‑93) have been described in various types of tissue injury and disease. However, the biological role of miR‑93 and its molecular mechanisms underlying the initiation and progression of ALI have not yet been reported, at least to the best of our knowledge. The present study aimed to investigate the regulatory effects exerted by miR‑93 in ALI. Using an in vivo murine model of ALI induced by lipopolysaccharide (LPS), miR‑93 expression was found to be downregulated in the lung tissues and bronchoalveolar lavage fluid (BALF) compared with the control group. Following agomiR‑93 injection, it was observed that agomiR‑93 attenuated lung injury, as evidenced by decreased lung permeability, a reduced lung wet/dry weight ratio and an increased survival rate of the mice. Concomitantly, agomiR‑93 significantly reduced LPS‑induced the interleukin (IL)‑6, IL‑1β, and tumor necrosis factor (TNF)‑α levels in BALF. Of note, Toll‑like receptor 4 (TLR4), an upstream regulator of the nuclear factor (NF)‑κB signaling pathway, was directly suppressed by miR‑93 in RAW 264.7 cells. Importantly, agomiR‑93 induced a significant suppression of the TLR4/myeloid differentiation primary response 88 (MyD88)/NF‑κB signaling pathway, as demonstrated by the downregulation of MyD88, and the phosphorylation of IκB‑α and p65 in the lung tissues of mice with ALI. Taken together, the findings of the present study indicate that miR‑93 attenutes LPS‑induced lung injury by regulating the TLR4/MyD88/NF‑κB signaling pathway, suggesting that miR‑93 may prove to be a potential therapeutic target for ALI.

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