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The Protective Effect of HBO1 on Cigarette Smoke Extract-Induced Apoptosis in Airway Epithelial Cells.

Abstract：

Purpose:Epigenetic modification is one of most important mechanisms underlying the pathogenesis of chronic obstructive pulmonary disease (COPD). The purpose of this study was to determine whether histone acetyltransferase binding to ORC1 (HBO1) can protect against cigarette smoke (CS)-induced cell apoptosis and sustain normal histone acetylation in COPD. Methods:Human lung tissue samples were obtained from patients who underwent lung resection. The emphysema mouse model and HBO1 overexpressing mice were each established by intraperitoneal injection with cigarette smoke extract (CSE) or intratracheal lentiviral vectors instillation. TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays were used to assess apoptotic ratio in mice. The apoptosis of human bronchial epithelial cells (HBECs) was assayed by flow cytometry. HBO1, B-cell lymphoma-2 (BCL-2), and H3K14ac protein expression were detected by Western blotting. HBO1 mRNA expression was measured by quantitative real-time polymerase chain reaction. Results:Protein expression of HBO1 was decreased significantly in lung tissue from COPD patients and CSE-treated emphysema mouse models. Overexpression of HBO1 attenuated CSE-induced emphysematous changes, as well as apoptosis in the lungs of COPD mice. In vitro, the HBO1 protein degraded in a time- and dose-dependent course with CSE treatment. With flow cytometry, we proved that HBO1 could reverse the apoptosis of HBECs induced by CSE. Furthermore, HBO1 overexpression promoted the expression of anti-apoptotic BCL-2 protein and enhanced H3K14 acetylation in airway epithelial cells. Conclusion:These findings demonstrate that the key histone modulator HBO1 plays a protective role in COPD pathogenesis that may shed light on potential therapeutic targets to inhibit the progress of COPD.

journal_name

Int J Chron Obstruct Pulmon Dis

journal_title

International journal of chronic obstructive pulmonary disease

authors

Chen L,Luo L,Kang N,He X,Li T,Chen Y

doi

10.2147/COPD.S234634

subject

Has Abstract

pub_date

2020-01-06 00:00:00

pages

15-24

eissn

1176-9106

issn

1178-2005

pii

234634

journal_volume

pub_type

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The Protective Effect of HBO1 on Cigarette Smoke Extract-Induced Apoptosis in Airway Epithelial Cells.