Advances in mechanisms and signaling pathways of idiopathic pulmonary fibrosis

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown etiology characterized by irreversible pulmonary tissue fibrosis, with a median survival of only 2-3 years and a poor prognosis. Recent studies have revealed abnormal activation of multiple signaling pathways in IPF pathogenesis, including TGF-β/Smad, Wnt/β-catenin, MAPK, and TIME pathways. Additionally, mechanisms such as redox imbalance, cellular senescence, metabolic reprogramming, and epigenetic dysregulation have been implicated in disease progression. Although FDA-approved pirfenidone and nintedanib can delay disease progression, they fail to reverse fibrotic lesions or significantly reduce mortality. This review systematically summarizes recent advances in IPF-related signaling pathways and molecular mechanisms, explores potential therapeutic targets, and evaluates lung transplantation as an end-stage intervention. Future research should focus on identifying novel molecular targets, developing targeted antifibrotic therapies, and optimizing lung transplantation eligibility assessments and perioperative management to advance precision medicine and improve patient outcomes. 31