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ETS1 Ameliorates Hyperoxia-Induced Alveolar Epithelial Cell Injury by Regulating the TGM2-Mediated Wnt/β-Catenin Pathway

  • HYPEROXIA-INDUCED LUNG INJURY
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Abstract

Purpose

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects newborns who need oxygen therapy, and high-concentration oxygen therapy may cause neonatal morbidity and mortality in newborns. E26 oncogene homologue 1 (ETS1) and transglutaminase 2 (TGM2) have been reported to be associated with lung cell injury. However, the mechanism of ETS1 in regulating BPD is still unclear.

Methods

Hyperoxia-induced A549 cells to simulate hyperoxia-induced alveolar epithelial cell injury. MTT assays and colony formation assays were performed to investigate the proliferation of A549 cells. Flow cytometry was carried out to quantify the apoptosis of A549 cells. The expression levels of ETS1 and TGM2 were quantified by qRT–PCR. The protein expression levels of ETS1, TGM2, β-catenin, c-Jun and MET were measured by western blot. Overexpression of ETS1, overexpression of TGM2, overexpression of ETS1 with downregulation of TGM2 and overexpression of TGM2 with inhibition of Wnt/β-catenin pathway were performed to investigate the role of ETS1, TGM2 and Wnt/β-catenin pathways in hyperoxia-induced alveolar epithelial cell injury.

Results

Hyperoxia decreased the proliferation and promoted the apoptosis of cells in a time-dependent manner. Moreover, overexpression of ETS1 rescued the effect of hyperoxia on proliferation and apoptosis. In addition, overexpression of TGM2 participated in the regulation of hyperoxia-induced proliferation and apoptosis. ETS1 regulated hyperoxia-induced alveolar epithelial cell injury through the Wnt/β-catenin pathway via TGM2.

Conclusion

ETS1 ameliorates hyperoxia-induced alveolar epithelial cell injury through the TGM2-mediated Wnt/β-catenin pathway.

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Data Availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

Code Availability

Not applicable.

Abbreviations

BPD:

Bronchopulmonary dysplasia

NCPAP:

Nasal continuous positive airway pressure

DMEM:

Dulbecco’s modified Eagle’s medium

FBS:

Fetal bovine serum

EST1 :

The E26 oncogene homolog 1

EBS:

ETS binding site

TGM2 :

Transglutaminase 2

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Funding

This work was supported by Youth Fund of Hunan Natural Science Foundation (No. 2019JJ50293) and Hunan Health Commission (No. B2019012).

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Authors and Affiliations

  1. Department of Respiratory, Hunan Children’s Hospital, No. 86 Ziyuan Road, Changsha, 410007, Hunan Province, China

    Min Yang, Yan-Ni Meng & Yan-Ping Chen

  2. Neonate Department, Hunan Children’s Hospital, Changsha, 410007, Hunan Province, China

    Xi-Rong Gao

  3. Research Institute of Children, Hunan Children’s Hospital, Changsha, 410007, Hunan Province, China

    Fang Shen

Authors
  1. Min Yang
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  2. Xi-Rong Gao
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  3. Yan-Ni Meng
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  4. Fang Shen
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Correspondence to Yan-Ping Chen.

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Supplementary Information

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408_2021_489_MOESM1_ESM.pdf

Supplementary file1 Schematic diagram: Hyperoxia-induced down-regulation of ETS1 affects the TGM2-mediated Wnt/β-catenin pathway, thereby promoting the apoptosis of alveolar epithelial cell injury and inhibiting proliferation (PDF 155 kb)

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Yang, M., Gao, XR., Meng, YN. et al. ETS1 Ameliorates Hyperoxia-Induced Alveolar Epithelial Cell Injury by Regulating the TGM2-Mediated Wnt/β-Catenin Pathway. Lung 199, 681–690 (2021). https://doi.org/10.1007/s00408-021-00489-9

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  • DOI: https://doi.org/10.1007/s00408-021-00489-9

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