TGF-β1 perturbs vascular development and inhibits epithelial differentiation in fetal lung in vivo
Article first published online: 25 MAY 2001
Copyright © 2001 Wiley-Liss, Inc.
Volume 221, Issue 3, pages 289–301, 1 July 2001
How to Cite
Zeng, X., Gray, M., Stahlman, M. T. and Whitsett, J. A. (2001), TGF-β1 perturbs vascular development and inhibits epithelial differentiation in fetal lung in vivo. Dev. Dyn., 221: 289–301. doi: 10.1002/dvdy.1140
- Issue published online: 15 JUN 2001
- Article first published online: 25 MAY 2001
- Manuscript Accepted: 15 FEB 2001
- Manuscript Received: 9 SEP 2000
- National Institutes of Health. Grant Number: HL51832
- Ryan Fellowship. Grant Number: HL38859
- surfactant proteins;
- lung morphogenesis;
- cell proliferation
Members of the transforming growth factor β (TGF-β) family of polypeptides have been implicated in morphogenesis and differentiation in numerous tissues, including the lung. In order to further define effects of TGF-β signaling in lung morphogenesis, a constitutively active form of TGF-β1 was expressed in respiratory epithelial cells of the fetal mouse lung in vivo. Expression of TGF-β1 arrested lung morphogenesis in the pseudoglandular stage of development, inhibiting synthesis of differentiation-dependent proteins, SP-B, SP-C, and CCSP, and maintaining embryonic patterns of staining for thyroid transcription factor-1 (TTF-1) and hepatocyte nuclear factor-3β (HNF-3β). The pulmonary mesenchyme was thickened and vascular density was increased by TGF-β1. TGF-β1 decreased expression of vascular endothelial growth factor-A (VEGF-A) mRNA and protein, and the abundance of Flk-1 mRNA in the lung mesenchyme. Distribution of platelet-endothelial cell adhesion molecule (PECAM)-1, a marker of pulmonary blood vessels, was altered, and ultrastructural studies demonstrated that TGF-β1 inhibited vascular development in the fetal lung. TGF-β1 perturbed both epithelial cell differentiation and formation of the pulmonary vasculature, supporting the concept that precise control of signaling via the TGF-β receptor pathway is critical for normal lung morphogenesis. © 2001 Wiley-Liss, Inc.