title: Alveolar epithelial disintegrity in pulmonary fibrosis.
abstract: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive decline in lung function, resulting in significant morbidity and mortality. Current concepts of the pathogenesis of IPF primarily center on dysregulated epithelial cell repair and altered epithelial-mesenchymal communication and extracellular matrix deposition following chronic exposure to cigarette smoke or environmental toxins. In recent years, increasing attention has been directed toward the role of the intercellular junctional complex in determining the specific properties of epithelia in pulmonary diseases. Additionally, recent genomewide association studies suggest that specific genetic variants predictive of epithelial cell dysfunction may confer susceptibility to the development of sporadic idiopathic pulmonary fibrosis. A number of genetic disorders linked to pulmonary fibrosis and familial interstitial pneumonias are associated with loss of epithelial integrity. However, the potential links between extrapulmonary clinical syndromes associated with defects in epithelial cells and the development of pulmonary fibrosis are not well understood. Here, we report a case of hereditary mucoepithelial dysplasia that presented with pulmonary fibrosis and emphysema on high-resolution computed tomography. This case illustrates a more generalizable concept of epithelial disintegrity in the development of fibrotic lung diseases, which is explored in greater detail in this review article.
authors.affiliation: Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Tejaswini
authors.identifier: http://orcid.org/0000-0002-4251-4988
authors.initials: T
authors.lastname: Kulkarni
authors.affiliation: Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Joao
authors.initials: J
authors.lastname: de Andrade
authors.affiliation: Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Tracy
authors.initials: T
authors.lastname: Luckhardt
authors.affiliation: Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama vjthan@uab.edu.
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Thannickal
mesh_terms: D000328:Adult; D056809:Alveolar Epithelial Cells / Q000473:pathology*; D002450:Cell Communication; D020022:Genetic Predisposition to Disease; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D008297:Male; D014057:Tomography, X-Ray Computed
keywords: cell-cell adhesion; epithelial barrier dysfunction; epithelial junctional complex; pulmonary fibrosis