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Am J Physiol Lung Cell Mol Physiol 285: L527-L539, 2003. First published February 21, 2003; doi:10.1152/ajplung.00298.2002
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EDITORIAL FOCUS

Release of biologically active TGF-{beta}1 by alveolar epithelial cells results in pulmonary fibrosis

Ying Dong Xu,1 Jiesong Hua,1 Alice Mui,2 Robert O'Connor,3 Gary Grotendorst,4 and Nasreen Khalil1

1Division of Respiratory Medicine, Department of Medicine, The University of British Columbia, and Vancouver Hospital; 2Department of Surgery and Vancouver Hospital, Vancouver V6H 3Z6; 3Department of Pathology, British Columbia Cancer Agency, Vancouver V5Z 4E6, British Columbia; and 4School of Medicine, University of Miami, Miami, Florida 33136

Submitted 29 August 2002 ; accepted in final form 14 February 2003

Idiopathic pulmonary fibrosis (IPF) is a progressive fatal fibrotic lung disease. Transforming growth factor (TGF)-{beta}1 is present in a biologically active conformation in the epithelial cells lining lesions with advanced IPF. To determine the role of aberrant expression of biologically active TGF-{beta}1 by alveolar epithelial cells (AECs), the AECs of explanted normal rat lungs were transfected with the TGF-{beta}1 gene using the retrovirus pMX-L-s223,225-TGF-{beta}1. In situ hybridization using a digoxigenin-labeled cDNA of the puromycin resistance gene contained in the pMX demonstrated that pMX-L-s233,225-TGF-{beta}1 was selectively transfected into AECs of the explants. Conditioned media overlying explants obtained 7 days after being treated with pMX-L-s223,225-TGF-{beta}1 contained 14.5 ± 3.15 pg/ml of active TGF-{beta}1. With the use of Masson's trichrome staining of explant sections obtained 14 days after transfection, there were lesions similar to those in IPF, characterized by type II AEC hyperplasia, interstitial thickening, extensive increase in interstitial and subepithelial collagen, an increase in the number of fibroblasts, and areas resembling fibroblast buds. Collagens I, III, IV, and V and fibronectin were increased in explants treated with pMX-L-s223,225-TGF-{beta}1. The findings in the current study suggest that IPF may be a disorder of epithelial cells and not inflammatory cells.

transforming growth factor-{beta}1; idiopathic pulmonary fibrosis


Address for reprint requests and other correspondence: Dr. N. Khalil, Division of Respiratory Medicine, Jack Bell Research Centre, 2660 Oak St., Vancouver, BC V6H 3Z6, Canada (E-mail: nkhalil{at}interchange.ubc.ca).




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