Valand Anita, Rajasekar Poojitha, Wain Louise V, Clifford Rachel L
Centre for Respiratory Research, Translational Medical Sciences, School of Medicine, University of Nottingham, UK; Nottingham NIHR Biomedical Research Centre, Nottingham, UK; Biodiscovery Institute, University Park, University of Nottingham, UK.
Department of Population Health Sciences, University of Leicester, Leicester, UK; NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK.
Int J Biochem Cell Biol. 2025 Mar;180:106739. doi: 10.1016/j.biocel.2025.106739. Epub 2025 Jan 21.
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.
肺纤维化，包括特发性肺纤维化（IPF），是一种复杂且具有破坏性的疾病，其特征是肺组织进行性瘢痕形成，导致呼吸功能受损。异常激活的成纤维细胞将细胞外基质成分沉积到周围的肺组织中，损害肺功能和气体交换能力。已发现遗传因素和表观遗传因素在肺纤维化的发病机制中均起作用，新出现的证据突出了这两种调节机制之间的相互作用。本综述概述了目前对肺纤维化中遗传学和表观遗传学之间相互作用的理解。我们讨论了与肺纤维化易感性相关的基因变异，并探讨了DNA甲基化、组蛋白修饰和非编码RNA表达等表观遗传修饰如何导致疾病。整合全基因组关联研究（GWAS）和表观基因组全关联研究（EWAS）的见解，以探索肺纤维化发病机制的分子机制。我们还讨论了遗传学和表观遗传学在肺纤维化中的潜在临床意义，包括新型治疗靶点的开发。总体而言，本综述强调了在理解和管理肺纤维化时考虑遗传因素和表观遗传因素的重要性。
