Interplay between genetics and epigenetics in lung fibrosis

Valand, Anita; Rajasekar, Poojitha; Wain, Louise V.; Clifford, Rachel L.

Abstract

Lung fibrosis, including idiopathic pulmonary fibrosis (IPF), is a complex and devastating disease characterised by the progressive scarring of lung tissue leading to compromised respiratory function. Aberrantly activated fibroblasts deposit extracellular matrix components into the surrounding lung tissue, impairing lung function and capacity for gas exchange. Both genetic and epigenetic factors have been found to play a role in the pathogenesis of lung fibrosis, with emerging evidence highlighting the interplay between these two regulatory mechanisms. This review provides an overview of the current understanding of the interplay between genetics and epigenetics in lung fibrosis. We discuss the genetic variants associated with susceptibility to lung fibrosis and explore how epigenetic modifications such as DNA methylation, histone modifications, and non-coding RNA expression contribute to disease. Insights from genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS) are integrated to explore the molecular mechanisms underlying lung fibrosis pathogenesis. We also discuss the potential clinical implications of genetics and epigenetics in lung fibrosis, including the development of novel therapeutic targets. Overall, this review highlights the importance of considering both genetic and epigenetic factors in the understanding and management of lung fibrosis.

Citation

Valand, A., Rajasekar, P., Wain, L. V., & Clifford, R. L. (2025). Interplay between genetics and epigenetics in lung fibrosis. International Journal of Biochemistry and Cell Biology, 180, Article 106739. https://doi.org/10.1016/j.biocel.2025.106739

• Journal Article Type: Review
• Acceptance Date: Jan 16, 2025
• Online Publication Date: Jan 21, 2025
• Publication Date: 2025-03
• Deposit Date: Jan 28, 2025
• Publicly Available Date: Jan 29, 2025
• Journal: International Journal of Biochemistry and Cell Biology
• Print ISSN: 1357-2725
• Electronic ISSN: 1878-5875
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 180
• Article Number: 106739
• DOI: https://doi.org/10.1016/j.biocel.2025.106739
• Keywords: Epigenetics, Genetics, DNA methylation, Lung, Fibrosis
• Public URL: https://nottingham-repository.worktribe.com/output/44538801
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S1357272525000068?via%3Dihub