Abhd2, a Candidate Gene Regulating Airway Remodeling in COPD via TGF-β

Abstract

Purpose

The typical characteristic of COPD is airway remodeling, affected by environmental and genetic factors. However, genetic studies on COPD have been limited. Currently, the Abhd2 gene is found to play a critical role in maintaining alveolar architecture and stability. The research aims to investigate the predictive value of Abhd2 for airway remodeling in COPD and its effect on TGF-β regulation.

Methods

In humans, Abhd2 protein was obtained from peripheral blood monocytes. Peripheral blood TGF-β, pulmonary surfactant proteins (SPs), metalloproteinases, inflammatory indicators (WBC, NEU, NLR, EOS, CRP, PCT, D-Dimer), chest CT (airway diameter and airway wall thickness), pulmonary function, and blood gas analysis were used to assess airway remodeling. In animals, Abhd2 deficient mice (Abhd2^Gt/Gt) using gene trapping and C57BL6 mice were injected intraperitoneally with CSE to construct COPD models. HE staining, Masson staining and immunohistochemistry were used to observe the pathological changes of airway in mice, and RT-PCR, WB, ELISA and immunofluorescence were used to detect the expression of secreted proteins and EMT markers.

Results

COPD patients with worse pulmonary function and higher airway remodeling-related inflammatory factors had lower Abhd2 protein expression. Moreover, indicators followed the same trend for COPD patients grouped by prognosis (Group A vs Group B). Serum TGF-β was negatively correlated with Abhd2 protein expression, FEV1/FVC, FEV1, and FEV1% PRED. In mice, Abhd2 depletion promoted deposition of TGF-β, leading to more pronounced emphysema, airway thickening, increased alveolar macrophage infiltration, decreased AECII number and SPs, and EMT phenomenon.

Conclusion

Downregulation of Abhd2 can promote airway remodeling in COPD by modulating repair after injury and EMT via TGF-β. This study suggests that Abhd2 may serve as a biomarker for assessing airway remodeling and guiding prognosis in COPD.

Keywords:

• alpha/beta hydrolase 2
• COPD
• TGF-β
• airway remodeling
• EMT

Data Sharing Statement

The data/documents could be obtained from corresponding author.

Ethics Approval

The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was approved by the institutional ethic committee of the Fourth Affiliated Hospital of Harbin Medical University (2022-SCILLSC-21) and informed consent was given by all patients. All animals were maintained and experimented in accordance with the ethical guidelines of the Guiding Principles in the Care and Use of Animals (China) and the Policy of Animal Care and Use Committee of the Fourth Affiliated Hospital of Harbin Medical University. All procedures were performed in accordance with the Declaration of Helsinki and relevant national policies.

Informed Consent

The information involved in the article has obtained all the patient’s oral informed consent.

Acknowledgments

This work was supported by the National Natural Science Foundation of China (81670028), Graduate Practice Innovation Project Fund of Harbin Medical University (2018182) and 2023 Scientific Research Project of Basic Scientific Research Business Fee of Provincial Institutions of Higher Education in Heilongjiang Province.

Disclosure

All authors indicate no conflict of interest in this work.