help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on August 27, 2004, doi:10.1165/rcmb.2004-0182OC

Am. J. Respir. Cell Mol. Biol., Volume 31, Number 6, December 2004, 679-686

A more recent version of this article appeared on December 1, 2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2004-0182OCv1
31/6/679    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhang, F.
Right arrow Articles by Mason, R. J
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhang, F.
Right arrow Articles by Mason, R. J

Submitted on June 8, 2004
Revised on August 27, 2004

TGF-{beta} antagonizes alveolar type II cell proliferation induced by KGF

Feijie Zhang1, Larry D Nielsen1, Joseph J Lucas1, and Robert J Mason1*

1 Departments of Medicine and Pediatrics, National Jewish Medical and Research Center, Denver, Colorado, USA

* To whom correspondence should be addressed. E-mail: masonb{at}njc.org.

Keratinocyte growth factor (KGF) is a mitogen for rat type II cells and also stimulates differentiation in vitro. Administration of KGF also protects the lung from a variety of injuries and subsequent development of fibrosis. Since TGF-{beta} has been shown to inhibit epithelial cell proliferation and surfactant protein gene expression in other systems and is thought to be a major effector in pulmonary fibrosis, we sought to determine if TGF-{beta} would antagonize the effects of KGF in primary cultures of alveolar type II cells. Type II cells were cultured on a matrix of type I collagen and Matrigel in the presence or absence of KGF and/or TGF-{beta}. KGF alone greatly stimulated proliferation and increased cdk2 kinase activity and Rb phosphorylation. Cyclin D1, cdk2, and cdc25A protein levels were increased, and p15Ink4b and p27Kip1 protein levels were decreased. TGF-{beta} markedly inhibited alveolar epithelial cell proliferation induced by KGF. TGF-{beta} inhibited cdk2 enzyme activity and Rb phosphorylation and increased p15Ink4b protein levels. TGF-{beta} also inhibited differentiation induced by KGF as measured by secretion of SP-A into the apical media. In summary, TGF-{beta} inhibits the proliferative effect of KGF in vitro and may be a biologic antagonist of KGF.




This article has been cited by other articles:


Home page
 Am. J. Respir. Cell Mol. Bio.Home page
R. Qiao, W. Yan, C. Clavijo, R. Mehrian-Shai, Q. Zhong, K.-J. Kim, D. Ann, E. D. Crandall, and Z. Borok
Effects of KGF on Alveolar Epithelial Cell Transdifferentiation Are Mediated by JNK Signaling
Am. J. Respir. Cell Mol. Biol., February 1, 2008; 38(2): 239 - 246.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Bhaskaran, N. Kolliputi, Y. Wang, D. Gou, N. R. Chintagari, and L. Liu
Trans-differentiation of Alveolar Epithelial Type II Cells to Type I Cells Involves Autocrine Signaling by Transforming Growth Factor beta1 through the Smad Pathway
J. Biol. Chem., February 9, 2007; 282(6): 3968 - 3976.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
M. A. Alejandre-Alcazar, G. Kwapiszewska, I. Reiss, O. V. Amarie, L. M. Marsh, J. Sevilla-Perez, M. Wygrecka, B. Eul, S. Kobrich, M. Hesse, et al.
Hyperoxia modulates TGF-beta/BMP signaling in a mouse model of bronchopulmonary dysplasia
Am J Physiol Lung Cell Mol Physiol, February 1, 2007; 292(2): L537 - L549.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
Y. Chang, J. Wang, X. Lu, D. P. Thewke, and R. J. Mason
KGF induces lipogenic genes through a PI3K and JNK/SREBP-1 pathway in H292 cells
J. Lipid Res., December 1, 2005; 46(12): 2624 - 2635.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2004 American Thoracic Society. 		  2009 ATS Conference