Epithelial-mesenchymal interactions in pulmonary fibrosis.
Pulmonary fibrosis represents the sequelae of a variety of acute and chronic lung injuries of known and unknown etiologies. Tissue specimens obtained from patients with pulmonary fibrosis, regardless of the etiology, consistently show evidence of an ongoing wound-repair response. Epithelial-mesenchymal interactions have critical roles in normal lung development, tissue repair processes, and fibrosis. Current hypotheses propose that dysregulated function of, and impaired communication between, epithelial and mesenchymal cells prevent resolution of the wound-repair response and contribute to the pathobiology of pulmonary fibrosis. This hypothesis is supported by abundant evidence from patients, animal models, and cell-culture studies demonstrating abnormalities in epithelial cell and mesenchymal cell activities including proliferation, differentiation, and survival. This article reviews the aberrant epithelial and mesenchymal cellular phenotypes found in the context of pulmonary fibrosis and discusses the mechanisms that perpetuate these cellular phenotypes.
Horowitz
Jeffrey C
JC
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA. jchorow@umich.edu
Thannickal
Victor J
VJ
D002450:Cell Communication; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000473:pathology*; D005109:Extracellular Matrix / Q000473:pathology; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D010641:Phenotype; D011658:Pulmonary Fibrosis / Q000473:pathology / Q000503:physiopathology*; D014945:Wound Healing