Pathological regulatory roles of lysine acylation modifications in idiopathic pulmonary fibrosis (Review)

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal interstitial lung disease pathologically defined by progressive fibrosing remodeling of the pulmonary interstitium and irreversible destruction of normal alveolar architecture. IPF has a complex pathogenesis involving three consecutive stages: Initial alveolitis, chronic fibrosis and end‑stage lung tissue destruction. Metabolic reprogramming is considered a key pathological feature throughout the disease process. Changes in the availability of intracellular metabolites caused by metabolic reprogramming may further influence the dynamic balance of acetylation modifications, thereby linking metabolic dysregulation to the fibrotic phenotype. However, its relationship with key pathological regulatory networks remains to be further elucidated. The present review summarizes seven acylation modifications in IPF, namely, lactylation, succinylation, acetylation, β‑hydroxybutyrylation, palmitoylation, citrullination and formylation, including their stage‑specific roles, crosstalk and therapeutic potential. The review further examines the links between different acylation modifications and metabolic reprogramming and fibrotic progression, identifies key regulatory nodes such as SIRT3 and establishes an integrated regulatory network of acylation modifications in IPF. By integrating the dynamic changes and crosstalk among distinct acylation modifications, the present review aims to advance our understanding of the metabolic‑acylation regulatory mechanisms underlying IPF and provide a theoretical basis for therapeutic approaches targeting acylation homeostasis.