Emerging concepts in the pathogenesis of lung fibrosis

WD Hardie, SW Glasser, JS Hagood - The American journal of pathology, 2009 - Elsevier
WD Hardie, SW Glasser, JS Hagood
The American journal of pathology, 2009Elsevier
Fibrogenesis is an often-deadly process with increasing world-wide incidence and limited
therapeutic options. Pulmonary fibrogenesis involves remodeling of the distal airspace and
parenchyma of the lung, and is characterized by excessive extracellular matrix deposition
and accumulation of apoptosis-resistant myofibroblasts. Recent studies have added
significantly to our understanding of the complex mechanisms involved in lung fibrogenesis.
Emerging concepts in this field include the critical role of the epithelium, particularly type II …
Fibrogenesis is an often-deadly process with increasing world-wide incidence and limited therapeutic options. Pulmonary fibrogenesis involves remodeling of the distal airspace and parenchyma of the lung, and is characterized by excessive extracellular matrix deposition and accumulation of apoptosis-resistant myofibroblasts. Recent studies have added significantly to our understanding of the complex mechanisms involved in lung fibrogenesis. Emerging concepts in this field include the critical role of the epithelium, particularly type II pneumocytes, in the initiation and perpetuation of fibrosis in response to either endogenous or exogenous stress; a growing awareness of alternative activation of macrophages in tissue remodeling; growing appreciation of the alternative origins and phenotypic plasticity of fibroblasts; the roles of epigenetic reprogramming and context-dependent signaling in profibrotic phenotype alterations; and recognition of the importance of cross talk and convergence of intracellular signaling pathways. In vitro, in vivo, and in silico approaches support a paradigm of “disordered re-development” of the lung. Designing effective antifibrotic interventions will require accurate understanding of the complex interactions among the genetic, environmental, epigenetic, biochemical, cellular, and contextual abnormalities that promote pulmonary fibrogenesis.
Elsevier