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

Abstract

Mei-Yu Lv,1,2 Ling-Ling Jin,2,3 Xi-Qiao Sang,2 Wen-Chao Shi,2 Li-Xia Qiang,2 Qing-Yan Lin,4 Shou-De Jin2 1Department of Respiratory Medicine, Harbin Medical University Cancer Hospital, Harbin, 150001, People’s Republic of China; 2Department of Respiratory Medicine, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China; 3Department of Critical Care medicine, the Second Affiliated Hospital of Xi ‘an Jiaotong University, Xi’an, Shaanxi, China; 4Department of Respiratory Medicine, Heilongjiang Provincial Hospital, Harbin, 150001, People’s Republic of ChinaCorrespondence: Shou-De Jin, Department of Respiratory Medicine, The Fourth Affiliated Hospital of Harbin Medical University, No. 37 Yiyuan Street, Nangang District, Harbin, 150001, People’s Republic of China, Tel/Fax [phone], Email [email protected]: 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 (Abhd2Gt/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

Keywords

• alpha/beta hydrolase 2
• copd
• tgf-β
• airway remodeling
• emt