title: Alveolar epithelial cells express mesenchymal proteins in patients with idiopathic pulmonary fibrosis.
abstract: Prior work has shown that transforming growth factor-β (TGF-β) can mediate transition of alveolar type II cells into mesenchymal cells in mice. Evidence this occurs in humans is limited to immunohistochemical studies colocalizing epithelial and mesenchymal proteins in sections of fibrotic lungs. To acquire further evidence that epithelial-to-mesenchymal transition occurs in the lungs of patients with idiopathic pulmonary fibrosis (IPF), we studied alveolar type II cells isolated from fibrotic and normal human lung. Unlike normal type II cells, type II cells isolated from the lungs of patients with IPF express higher levels of mRNA for the mesenchymal proteins type I collagen, α-smooth muscle actin (α-SMA), and calponin. When cultured on Matrigel/collagen, human alveolar type II cells maintain a cellular morphology consistent with epithelial cells and expression of surfactant protein C (SPC) and E-cadherin. In contrast, when cultured on fibronectin, the human type II cells flatten, spread, lose expression of pro- SPC, and increase expression of vimentin, N-cadherin, and α-SMA; markers of mesenchymal cells. Addition of a TGF-β receptor kinase inhibitor (SB431542) to cells cultured on fibronectin inhibited vimentin expression and maintained pro-SPC expression, indicating persistence of an epithelial phenotype. These data suggest that alveolar type II cells can acquire features of mesenchymal cells in IPF lungs and that TGF-β can mediate this process.
authors.affiliation: Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco, California 94143-0111, USA.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Marmai
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Sutherland
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Kim
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Dolganov
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Fang
authors.forename: Sophia S
authors.initials: SS
authors.lastname: Kim
authors.forename: Shuwei
authors.initials: S
authors.lastname: Jiang
authors.forename: Jeffery A
authors.initials: JA
authors.lastname: Golden
authors.forename: Charles W
authors.initials: CW
authors.lastname: Hoopes
authors.forename: Michael A
authors.initials: MA
authors.lastname: Matthay
authors.forename: Harold A
authors.initials: HA
authors.lastname: Chapman
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Wolters
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002469:Cell Separation; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005353:Fibronectins / Q000494:pharmacology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics* / Q000473:pathology; D007150:Immunohistochemistry; D007834:Lasers; D008648:Mesoderm / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D042282:Microdissection; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D005353:Fibronectins; D011506:Proteins; D016212:Transforming Growth Factor beta