Low TET1 Expression Levels in COPD Are Associated with Airway and Blood Neutrophilia.

Hong Ji, Xue Zhang, Angela L Linderholm, Maya Juarez, Michael Schivo, Brooks Kuhn, Richart W Harper, Amir A Zeki, Angela Haczku
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Abstract

Epigenetic dysregulation, particularly DNA methylation variations, is implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Ten-eleven translocation (TET) proteins (TET1, TET2, and TET3) regulate DNA methylation and gene transcription. Impaired TET1 expression was previously associated with airway inflammation and asthma. Here we investigated TET gene associations with COPD severity. We found that reduced TET1 expression in peripheral blood mononuclear cells was associated with higher sputum and blood neutrophil counts, decreased lung function and increased disease severity in patients. These findings support a potential protective role and warrant further mechanistic investigations into the actions of TET1 in COPD.

COPD患者TET1低表达水平与气道和血液中性粒细胞增多有关
表观遗传失调,特别是DNA甲基化变异,与慢性阻塞性肺疾病(COPD)的发病机制有关。10 - 11易位(TET)蛋白(TET1, TET2和TET3)调节DNA甲基化和基因转录。先前,TET1表达受损与气道炎症和哮喘有关。在这里,我们研究TET基因与COPD严重程度的关系。我们发现外周血单个核细胞中TET1表达降低与患者痰和血液中性粒细胞计数升高、肺功能下降和疾病严重程度增加有关。这些发现支持了TET1在COPD中的潜在保护作用,并为进一步研究TET1在COPD中的作用提供了依据。
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