Idiopathic Pulmonary Fibrosis: An Update on Pathogenesis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive, lethal fibrotic lung disease that occurs primarily in middle-aged and elderly adults. It is a major cause of morbidity and mortality. With an increase in life expectancy, the economic burden of IPF is expected to continuously rise in the near future. Although the exact pathophysiological mechanisms underlying IPF remain not known. Significant progress has been made in our understanding of the pathogenesis of this devastating disease in last decade. The current paradigm assumes that IPF results from sustained or repetitive lung epithelial injury and subsequent activation of fibroblasts and myofibroblast differentiation. Persistent myofibroblast phenotype contributes to excessive deposition of the extracellular matrix (ECM) and aberrant lung repair, leading to tissue scar formation, distortion of the alveolar structure, and irreversible loss of lung function. Treatments of patients with IPF by pirfenidone and nintedanib have shown significant reduction of lung function decline and slowing of disease progression in patients with IPF. However, these drugs do not cure the disease. In this review, we discuss recent advances on the pathogenesis of IPF and highlight the development of novel therapeutic strategies against the disease.

Targeting Growth Factor and Cytokine Pathways to Treat Idiopathic Pulmonary Fibrosis

“…Although the pathophysiological mechanism of IPF remains unknown, significant progress in understanding the pathogenesis of IPF has been made in the last decade. The current paradigm assumes that recurrent alveolar epithelial cell injury and the crosstalk between dysregulated epithelial cells and mesenchymal, immune, endothelial cells can trigger abnormal wound healing responses and pulmonary fibrosis via multiple signaling pathways- (Mei et al, 2021;Moss et al, 2022). The pathogenesis of IPF is believed to be mediated by various cytokines, chemokines, and growth factors (Kelly et al, 2003).…”

Research Progress of Fibroblast Growth Factor 21 in Fibrotic Diseases

“…Since its broad impact and serious consequences, fibrosis has become one of the leading global healthcare issues [ 6 ]. Despite a host of promising experimental data in the animal model, there are very few approved antifibrotic drugs that show significant effects on ameliorating or delaying the disease progression [ 20 – 22 ].…”

Mesenchyme Stem Cell-Derived Conditioned Medium as a Potential Therapeutic Tool in Idiopathic Pulmonary Fibrosis

“…Although idiopathic interstitial pneumonia, in one or another form, has been described since the late 19th century and the IPF has been known since the mid-20th century, only recently have we made progress in understanding the pathogenesis of the disease, and new antifibrotic agents have been in use, which can only attenuate symptoms and slow the progression of fibrosis [ 12 , 23 , 40 ]. It is recognized that none of the existing treatments can combat the pathogenic mechanisms of the disease, preventing fibrosis and significantly prolonging survival after diagnosis.…”