The Notch pathway attenuates burn-induced acute lung injury in rats by repressing reactive oxygen species

Weixia Cai; Kuo Shen; Peng Ji; Yanhui Jia; Shichao Han; Wanfu Zhang; Xiaolong Hu; Xuekang Yang; Juntao Han; Dahai Hu

doi:10.1093/burnst/tkac008

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The Notch pathway attenuates burn-induced acute lung injury in rats by repressing reactive oxygen species

更新时间：2022-06-09

- The Notch pathway attenuates burn-induced acute lung injury in rats by repressing reactive oxygen species
- The Notch pathway attenuates burn-induced acute lung injury in rats by repressing reactive oxygen species
- Burns & Trauma 2022年10卷第1期
- 作者机构：
  
  1. Department of Burns and Cutaneous Surgery
  2. Fourth Military Medical University
- 作者简介：
- 基金信息：
  
  This work was supported by grants from the National Natural Science Foundation of China (81601680 and 81671910).
- DOI：10.1093/burnst/tkac008
  中图分类号：
- 纸质出版日期：2022，
  
  网络出版日期：2022-4-12，
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The Notch pathway attenuates burn-induced acute lung injury in rats by repressing reactive oxygen species[J]. Burns & Trauma, 2022,10(1).

Weixia Cai, Kuo Shen, Peng Ji, Yanhui Jia, Shichao Han, Wanfu Zhang, Xiaolong Hu, Xuekang Yang, Juntao Han, Dahai Hu, The Notch pathway attenuates burn-induced acute lung injury in rats by repressing reactive oxygen species, Burns & Trauma, Volume 10, 2022, tkac008, https://doi.org/10.1093/burnst/tkac008
The Notch pathway attenuates burn-induced acute lung injury in rats by repressing reactive oxygen species[J]. Burns & Trauma, 2022,10(1). DOI： 10.1093/burnst/tkac008.

Weixia Cai, Kuo Shen, Peng Ji, Yanhui Jia, Shichao Han, Wanfu Zhang, Xiaolong Hu, Xuekang Yang, Juntao Han, Dahai Hu, The Notch pathway attenuates burn-induced acute lung injury in rats by repressing reactive oxygen species, Burns & Trauma, Volume 10, 2022, tkac008, https://doi.org/10.1093/burnst/tkac008 DOI：

摘要

Abstract

BackgroundAcute lung injury (ALI) is a common complication following severe burns. The underlying mechanisms of ALI are incompletely understood; thus

available treatments are not sufficient to repair the lung tissue after ALI.MethodsTo investigate the relationship between the Notch pathway and burn-induced lung injury

we established a rat burn injury model by scalding and verified lung injury via lung injury evaluations

including hematoxylin and eosin (H&E) staining

lung injury scoring

bronchoalveolar lavage fluid and wet/dry ratio analyses

myeloperoxidase immunohistochemical staining and reactive oxygen species (ROS) accumulation analysis. To explore whether burn injury affects Notch1 expression

we detected the expression of Notch1 and Hes1 after burn injury. Then

we extracted pulmonary microvascular endothelial cells (PMVECs) and conducted Notch pathway inhibition and activation experiments

via a γ-secretase inhibitor (GSI) and OP9-DLL1 coculture

respectively

to verify the regulatory effect of the Notch pathway on ROS accumulation and apoptosis in burn-serum-stimulated PMVECs. To investigate the regulatory effect of the Notch pathway on ROS accumulation

we detected the expression of oxidative-stress-related molecules such as superoxide dismutase

nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) 2

NOX4 and cleaved caspase-3. NOX4-specific small interfering RNA (siRNA) and the inhibitor GKT137831 were used to verify the regulatory effect of the Notch pathway on ROS via NOX4.ResultsWe successfully established a burn model and revealed that lung injury

excessive ROS accumulation and an inflammatory response occurred. Notch1 detection showed that the expression of Notch1 was significantly increased after burn injury. In PMVECs challenged with burn serum

ROS and cell death were elevated. Moreover

when the Notch pathway was suppressed by GSI

ROS and cell apoptosis levels were significantly increased. Conversely

these parameters were reduced when the Notch pathway was activated by OP9-DLL1. Mechanistically

the inhibition of NOX4 by siRNA and GKT137831 showed that the Notch pathway reduced ROS production and cell apoptosis by downregulating the expression of NOX4 in PMVECs.ConclusionsThe Notch pathway reduced ROS production and apoptosis by downregulating the expression of NOX4 in burn-stimulated PMVECs. The Notch–NOX4 pathway may be a novel therapeutic target to treat burn-induced ALI.

关键词

Keywords

Acute lung injuryNotch pathwayReactive oxygen speciesPulmonary microvascular endothelial cellsNicotinamide adenine dinucleotide phosphate oxidase 4Burn

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