Bioinformatic Analysis of ABCA1 Gene Expression in Smoking and Chronic Obstructive Pulmonary Disease.

Stanislav Kotlyarov,Anna Kotlyarova

doi:10.3390/membranes11090674

Abstract

Smoking is a key modifiable risk factor for developing the chronic obstructive pulmonary disease (COPD). When smoking, many processes, including the reverse transport of cholesterol mediated by the ATP binding cassette transporter A1 (ABCA1) protein are disrupted in the lungs. Changes in the cholesterol content in the lipid rafts of plasma membranes can modulate the function of transmembrane proteins localized in them. It is believed that this mechanism participates in increasing the inflammation in COPD. Methods: Bioinformatic analysis of datasets from Gene Expression Omnibus (GEO) was carried out. Gene expression data from datasets of alveolar macrophages and the epithelium of the respiratory tract in smokers and COPD patients compared with non-smokers were used for the analysis. To evaluate differentially expressed genes, bioinformatic analysis was performed in comparison groups using the limma package in R (v. 4.0.2), and the GEO2R and Phantasus tools (v. 1.11.0). Results: The conducted bioinformatic analysis showed changes in the expression of the ABCA1 gene associated with smoking. In the alveolar macrophages of smokers, the expression levels of ABCA1 were lower than in non-smokers. At the same time, in most of the airway epithelial datasets, gene expression did not show any difference between the groups of smokers and non-smokers. In addition, it was shown that the expression of ABCA1 in the epithelial cells of the trachea and large bronchi is higher than in small bronchi. Conclusions: The conducted bioinformatic analysis showed that smoking can influence the expression of the ABCA1 gene, thereby modulating lipid transport processes in macrophages, which are part of the mechanisms of inflammation development.

Highlights

According to rough estimates, more than a billion people smoke in the world [1,2,3]
The conducted bioinformatic analysis of the data sets of alveolar macrophages (GSE13896 and GSE130928) showed that smoking alters the expression of the ATP binding cassette transporter A1 (ABCA1) gene
No differences in the expression of ABCA1 were found in smokers and patients with chronic obstructive pulmonary disease (COPD)

Summary

Introduction

More than a billion people smoke in the world [1,2,3]. Smoking is the main cause of the chronic obstructive pulmonary disease (COPD), the medical and social significance of which is steadily increasing [4,5]. The pathogenesis of COPD is based on inflammation in the bronchi, in which many cells are involved. Macrophages play an important role in the development and progression of COPD [10,11,12]. These cells are heterogeneous in their functions and demonstrate both pro- and anti-inflammatory activity, participate in the production of many humoral factors, recruit other cells. It is believed that the heterogeneity of macrophages is based on the peculiarities of their carbohydrate and lipid metabolism [13,14,15,16,17,18,19]

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