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Review
. 2006 Dec;27(6):600-12.
doi: 10.1055/s-2006-957332.

Epithelial-mesenchymal interactions in pulmonary fibrosis

Jeffrey C Horowitz  1 , Victor J Thannickal
Affiliations
Review

Epithelial-mesenchymal interactions in pulmonary fibrosis

Jeffrey C Horowitz et al. Semin Respir Crit Care Med. 2006 Dec.

Abstract

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.

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Figures

Figure 1
Figure 1
Schematic representation of epithelial and mesenchymal cell phenotypes and their interactions in the context of pulmonary fibrosis. Epithelial cells overlying damaged basement membrane and fibroblastic foci demonstrate phenotypes suggestive of a dysregulated wound-repair response, including excessive apoptosis, dysregulated proliferation, and impaired migration and regeneration. In contrast, underlying mesenchymal cells demonstrate myofibroblast differentiation, resistance to apoptosis, proliferation and secretion of soluble factors, extracellular matrix (ECM) proteins, and oxidants. Both epithelial and mesenchymal cells secrete soluble mediators that function through paracrine and autocrine mechanisms to regulate cell phenotypes. Additionally, the ECM provides a substrate for epithelial–mesenchymal interactions and may also directly regulate epithelial and mesenchymal cell phenotypes.
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