Epithelium-dependent profibrotic milieu in the pathogenesis of idiopathic pulmonary fibrosis: current status and future directions.

BACKGROUND AND AIM: Idiopathic pulmonary fibrosis (IPF) is characterized by hyperplasia of type II alveolar epithelial cells, aggregation of activated (myo)fibroblasts and excessive deposition of extracellular matrix, which will ultimately lead to lung architecture destruction with no proven effective therapies. Despite a significant increase in our understanding on the etiology and pathogenesis of IPF, the real triggers that initiate epithelial cell injury and promote fibrosis evolution are still elusive. We wanted to discuss the evolution of hypothesis on IPF pathogenesis and to suggest some new directions which need to be further elucidated.

METHODS: We have done a literature search in PubMed database by using the term 'idiopathic pulmonary fibrosis' AND (pathogenesis OR inflammation OR wound healing OR apoptosis OR extracellular matrix OR animal model).

RESULTS: Inflammatory hypothesis had been the dominant idea for several decades which suggests that chronic inflammation drives the onset and advance of the fibrotic process. However, it is seriously challenged nowadays because lung tissues from IPF patients exhibit little inflammatory lesions. Also, anti-inflammation therapy failed to exert a beneficial effect to IPF patients. Furthermore, experimental lung fibrosis can be realized independent of inflammation. Today, modern paradigm suggests that IPF is mainly driven by the profibtic milieu formed by epithelial injury/ disability and dysregulated epithelial mesenchymal interaction.

CONCLUSIONS: Epithelium-dependent profibrotic milieu formation and mesenchymal activation is the current view on the pathogenesis of IPF. New evidence from more analogous animal models may emerge and shift our thinking to a new and more faithful concept in the future.