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Respiratory Research
Published in: Respiratory Research 1/2022

01-12-2022 | Chronic Obstructive Lung Disease | Research

Protein interaction networks provide insight into fetal origins of chronic obstructive pulmonary disease

Authors: Annika Röhl, Seung Han Baek, Priyadarshini Kachroo, Jarrett D. Morrow, Kelan Tantisira, Edwin K. Silverman, Scott T. Weiss, Amitabh Sharma, Kimberly Glass, Dawn L. DeMeo

Published in: Respiratory Research | Issue 1/2022

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Abstract

Background

Chronic obstructive pulmonary disease (COPD) is a leading cause of death in adults that may have origins in early lung development. It is a complex disease, influenced by multiple factors including genetic variants and environmental factors. Maternal smoking during pregnancy may influence the risk for diseases during adulthood, potentially through epigenetic modifications including methylation.

Methods

In this work, we explore the fetal origins of COPD by utilizing lung DNA methylation marks associated with in utero smoke (IUS) exposure, and evaluate the network relationships between methylomic and transcriptomic signatures associated with adult lung tissue from former smokers with and without COPD. To identify potential pathobiological mechanisms that may link fetal lung, smoke exposure and adult lung disease, we study the interactions (physical and functional) of identified genes using protein–protein interaction networks.

Results

We build IUS-exposure and COPD modules, which identify connected subnetworks linking fetal lung smoke exposure to adult COPD. Studying the relationships and connectivity among the different modules for fetal smoke exposure and adult COPD, we identify enriched pathways, including the AGE-RAGE and focal adhesion pathways.

Conclusions

The modules identified in our analysis add new and potentially important insights to understanding the early life molecular perturbations related to the pathogenesis of COPD. We identify AGE-RAGE and focal adhesion as two biologically plausible pathways that may reveal lung developmental contributions to COPD. We were not only able to identify meaningful modules but were also able to study interconnections between smoke exposure and lung disease, augmenting our knowledge about the fetal origins of COPD.
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Metadata
Title
Protein interaction networks provide insight into fetal origins of chronic obstructive pulmonary disease
Authors
Annika Röhl
Seung Han Baek
Priyadarshini Kachroo
Jarrett D. Morrow
Kelan Tantisira
Edwin K. Silverman
Scott T. Weiss
Amitabh Sharma
Kimberly Glass
Dawn L. DeMeo
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2022
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-022-01963-5

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WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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