Pathogenetic mechanisms of idiopathic pulmonary fibrosis: A modern view on the role of genetic and epigenetic factors

ntroduction. Idiopathic pulmonary fibrosis is one of the most complex and understudied diseases of the pulmonary system. This pathological process is characterized by progressive lung tissue fibrosis leading to the irreversible deterioration of respiratory function and a significant reduction in patients’ quality of life. In recent decades, there is an increase in the incidence of idiopathic pulmonary fibrosis observed, highlighting the need for an in-depth study of its pathogenesis. Despite significant advances in the diagnosis and treatment of respiratory diseases, the pathogenesis of idiopathic pulmonary fibrosis remains understudied. Modern research focuses on the molecular and cellular mechanisms underlying this disease, including genetic and epigenetic factors that may play a key role in its development and progression. Aim. To provide up-to-date information on idiopathic pulmonary fibrosis and analyze the latest existing data regarding the role of genetic and epigenetic mechanisms in the pathogenesis of idiopathic pulmonary fibrosis in 2008–2025. Genetic and epigenetic factors were chosen for investigation in this review due to their significant impact on the molecular mechanisms underlying idiopathic pulmonary fibrosis. Materials and Methods. The literature search was conducted according to the PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Selection was only carried out among original articles and reviews in Russian and English. 497 publications were identified. Publications included in the review: n=66. Publications excluded due to not meeting the inclusion criteria: n=431. Results and Discussion. The analysis performed showed that IPF results from a complex interaction of genetic predisposition, environmental factors, and epigenetic changes. It was established that a key role in the pathogenesis is played by repeated damage to the alveolar epithelium and its pathological reprogramming according to the “double-hit” hypothesis mechanism. Hereditary risks are largely determined by the polymorphism of the MUC5B gene and mutations in telomere and surfactant protein genes, leading to cellular senescence and impaired repair. These processes trigger a cascade of fibrogenic reactions, including the epithelial-mesenchymal transition and excessive deposition of extracellular matrix. The data obtained underscore idiopathic pulmonary fibrosis as a multifactorial disease. Conclusions. Genetic mutations and polymorphisms can determine predisposition to the disease, while epigenetic changes regulate gene expression, influencing the development and progression of fibrotic processes in the lungs.