Alveolar epithelial cells express mesenchymal proteins in patients with idiopathic pulmonary fibrosis

作者：Marmai Cecilia; Sutherland Rachel E; Kim Kevin K; Dolganov Gregory M; Fang Xiaohui; Kim Sophia S; Jiang Shuwei; Golden Jeffery A; Hoopes Charles W; Matthay Michael A; Chapman Harold A; Wolters Paul J^*

来源：American Journal of Physiology - Lung Cellular and Molecular Physiology, 2011, 301(1): L71-L78.

DOI：10.1152/ajplung.00212.2010

• fibronectin
• usual interstitial pneumonia
• flow cytometry
• epithelial-to-mesenchymal transition

Marmai C, Sutherland RE, Kim KK, Dolganov GM, Fang X, Kim SS, Jiang S, Golden JA, Hoopes CW, Matthay MA, Chapman HA, Wolters PJ. Alveolar epithelial cells express mesenchymal proteins in patients with idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 301: L71-L78, 2011. First published April 15, 2011; doi: 10.1152/ajplung.00212.2010.-Prior work has shown that transforming growth factor-beta (TGF-beta) 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, alpha-smooth muscle actin (alpha-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 alpha-SMA; markers of mesenchymal cells. Addition of a TGF-beta 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-beta can mediate this process.

• 出版日期2011-7