Aberrant glycosylation in pulmonary fibrosis: Mechanisms, biomarkers, and treatment opportunities.

Fibrosis is characterized by excessive accumulation of scar tissue extending beyond the physiological healing process, ultimately leading to tissue damage and organ dysfunction. In many industrialized countries, fibrosis is a leading cause of mortality, contributing to approximately 45 % of deaths. Despite considerable advances in elucidating its underlying molecular and cellular mechanisms, current therapeutic strategies remain largely limited to palliative care. Consequently, there is an urgent demand for the identification of novel therapeutic targets in the clinical management of fibrosis and the development of effective anti-fibrotic agents. Both clinical observations and experimental models underscore the multifaceted nature of fibrotic disorders, which contributes to the complexity of treatment. Recent investigations have focused on the epigenetic regulation, particularly post-translational modifications (PTMs), in the pathogenesis and potential treatment of fibrosis. PTMs, including glycosylation, acetylation, phosphorylation, and methylation, induce subtle yet functionally impactful alterations in protein structure and activity. Among these, glycosylation has garnered increasing attention due to its demonstrated therapeutic relevance in various pathological contexts, including cancer, chronic inflammation, and neurodegenerative diseases. Accumulating evidence now indicates that glycosylation plays a pivotal role in the initiation and progression of fibrosis. Technological advances in glycomics and glycoproteomics have substantially deepened our understanding of how glycosylation modulates the fibrotic processes. This review focuses on the role of protein glycosylation in pulmonary fibrosis, highlighting distinct glycosylation patterns and enzymatic alterations implicated in disease progression. Furthermore, it explores the potential of glycosylation-based biomarkers and therapeutic interventions, emphasizing its promise for improving clinical diagnosis and treatment strategies in fibrotic pathologies.