AKR1C1 alleviates LPS‑induced ALI in mice by activating the JAK2/STAT3 signaling pathway

Wang,Xianjun; Yang,Baocheng; Li,Yuyu; Luo,Jiye; Wang,Yanli

doi:10.3892/mmr.2021.12473

AKR1C1 alleviates LPS‑induced ALI in mice by activating the JAK2/STAT3 signaling pathway

Authors:
- Xianjun Wang
- Baocheng Yang
- Yuyu Li
- Jiye Luo
- Yanli Wang
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Affiliations: Emergency Observation Ward, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu 222002, P.R. China, Emergency Medicine Department, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu 222002, P.R. China, Emergency Medicine Department, The First People's Hospital of Lianyungangy, Lianyungang, Jiangsu 222002, P.R. China
Published online on: September 30, 2021 https://doi.org/10.3892/mmr.2021.12473
Article Number: 833
Copyright: © Wang 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 respiratory tract disease characterized by increased alveolar/capillary permeability, lung inflammation and structural damage to lung tissues, which can progress and transform into acute respiratory distress syndrome (ARDS). Although there are several treatment strategies available to manage this condition, there is still no specific cure for ALI. Aldo‑keto reductase family 1 member C1 (AKR1C1) is a member of the aldo‑keto reductase superfamily, and is a well‑known Nrf2 target gene and an oxidative stress gene. The aim of the present study was to investigate the effects of AKR1C1 on a lipopolysaccharide (LPS)‑induced ALI model. After mice received LPS treatment, the mRNA expression levels of AKR1C1 in the bronchoalveolar lavage fluid and serum were measured using reverse transcription‑quantitative PCR and its relationship with the inflammatory factors and malondialdehyde levels were determined using correlation analysis. Next, AKR1C1 was overexpressed or knocked out in mice, and subsequently ALI was induced in mice using LPS. The severity of ALI, oxidative stress and inflammation in the lungs were measured, and the potential involvement of the Janus kinase 2 (JAK2)/signal transduction activator of transcription 3 (STAT3) signaling pathway was assessed by measuring the changes of lung injury parameters after the agonists of JAK2/STAT3 pathway, including interleukin (IL)‑6 and colivelin, were administrated to mice. The results revealed that AKR1C1 expression was decreased in the LPS‑induced ALI mouse model. AKR1C1 expression was inversely correlated with serum tumor necrosis factor‑α, IL‑6 and malondialdehyde levels, and positively correlated with serum IL‑10 levels. AKR1C1 overexpression significantly attenuated lung injury, as shown by the changes in Evans blue leakage in the lung, lung wet/dry weight ratio, PaO₂/FIO₂ ratio, survival rate of mice and histological lung changes. In addition, the JAK2/STAT3 signaling pathway was significantly deactivated by AKR1C1^+/+. When AKR1C1^+/+ mice were treated with JAK2/STAT3 agonists, the effects of AKR1C1 overexpression on lung injury and oxidative stress were abolished. In conclusion, AKR1C1 may protect against oxidative stress and serve as a negative regulator of inflammation in ALI/ARDS. In addition, the JAK2/STAT3 signaling pathway could participate in the protective effects of AKR1C1 against ALI.

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