QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 11 March 2008
doi: 10.1242/jcs.019455

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: jcs.019455v1 121/7/1036    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Alcorn, J. F. Articles by Janssen-Heininger, Y. M. W. Search for Related Content PubMed PubMed Citation Articles by Alcorn, J. F. Articles by Janssen-Heininger, Y. M. W. Social Bookmarking                         What's this?

Jun N-terminal kinase 1 regulates epithelial-to-mesenchymal transition induced by TGF-β1

¹ Department of Pathology, University of Vermont, Burlington, VT 05405, USA
² Department of Medicine, University of Vermont, Burlington, VT 05405, USA
³ Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA

^* Author for correspondence (e-mail: yvonne.janssen{at}uvm.edu)

Accepted 10 January 2008

Transforming growth factor β1 (TGF-β1) is a cardinal cytokine in the pathogenesis of airway remodeling, and promotes epithelial-to-mesenchymal transition (EMT). As a molecular interaction between TGF-β1 and Jun N-terminal kinase (JNK) has been demonstrated, the goal of this study was to elucidate whether JNK plays a role in TGF-β1-induced EMT. Primary cultures of mouse tracheal epithelial cells (MTEC) from wild-type, JNK1^–/– or JNK2^–/– mice were comparatively evaluated for their ability to undergo EMT in response to TGF-β1. Wild-type MTEC exposed to TGF-β1 demonstrated a prominent induction of mesenchymal mediators and a loss of epithelial markers, in conjunction with a loss of trans-epithelial resistance (TER). Significantly, TGF-β1-mediated EMT was markedly blunted in epithelial cells lacking JNK1, while JNK2^–/– MTEC underwent EMT in response to TGF-β1 in a similar way to wild-type cells. Although Smad2/3 phosphorylation and nuclear localization of Smad4 were similar in JNK1^–/– MTEC in response to TGF-β1, Smad DNA-binding activity was diminished. Gene expression profiling demonstrated a global suppression of TGF-β1-modulated genes, including regulators of EMT in JNK1^–/– MTEC, in comparison with wild-type cells. In aggregate, these results illuminate the novel role of airway epithelial-dependent JNK1 activation in EMT.

Key words: Lung, EMT, TGF-β, JNK, SMAD, Mouse

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				A. N. Abell, D. A. Granger, N. L. Johnson, N. Vincent-Jordan, C. F. Dibble, and G. L. Johnson Trophoblast Stem Cell Maintenance by Fibroblast Growth Factor 4 Requires MEKK4 Activation of Jun N-Terminal Kinase Mol. Cell. Biol., May 15, 2009; 29(10): 2748 - 2761. [Abstract] [Full Text] [PDF]

				S. Matalon and K. B. Adler Highlights of the April Issue Am. J. Respir. Cell Mol. Biol., April 1, 2009; 40(4): 383 - 384. [Full Text] [PDF]

				J. F. Alcorn, J. van der Velden, A. L. Brown, B. McElhinney, C. G. Irvin, and Y. M. W. Janssen-Heininger c-Jun N-Terminal Kinase 1 Is Required for the Development of Pulmonary Fibrosis Am. J. Respir. Cell Mol. Biol., April 1, 2009; 40(4): 422 - 432. [Abstract] [Full Text] [PDF]

				N. Garamszegi, S. P. Garamszegi, L. A. Shehadeh, and S. P. Scully Extracellular Matrix-Induced Gene Expression in Human Breast Cancer Cells Mol. Cancer Res., March 1, 2009; 7(3): 319 - 329. [Abstract] [Full Text] [PDF]