JBC PeproTech; Our Business is Cytokines!

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M101840200 on May 3, 2001

J. Biol. Chem., Vol. 276, Issue 26, 24414-24421, June 29, 2001
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
276/26/24414    most recent
M101840200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
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 Smart, D. E.
Right arrow Articles by Mann, D. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Smart, D. E.
Right arrow Articles by Mann, D. A.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

JunD Regulates Transcription of the Tissue Inhibitor of Metalloproteinases-1 and Interleukin-6 Genes in Activated Hepatic Stellate Cells*

David E. SmartDagger , Karen J. VincentDagger , Michael J. P. ArthurDagger , Oliver Eickelberg§, Marc Castellazzi, Jelena MannDagger , and Derek A. MannDagger ||

From the Dagger  Liver Group, Division of Infection, Inflammation, and Repair, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, United Kingdom, the § Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520-8023, and the  Unité de Virologie Humaine, INSERM U412, Ecole Normale Supérieure, 69364 Lyon Cedex 07, France

Activation of hepatic stellate cells (HSCs) to a myofibroblast-like phenotype is the pivotal event in hepatic wound healing and fibrosis. Rat HSCs activated in vitro express JunD, Fra2, and FosB as the predominant AP-1 DNA-binding proteins, and all three associate with an AP-1 sequence that is essential for activity of the tissue inhibitor of metalloproteinases-1 (TIMP-1) promoter. In this study, we used expression vectors for wild-type, dominant-negative, and forced homodimeric (Jun/eb1 chimeric factors) forms of JunD and other Fos and Jun proteins to determine the requirement for JunD in the transcriptional regulation of the TIMP-1 and interleukin-6 (IL-6) genes. JunD activity was required for TIMP-1 gene promoter activity, whereas overexpression of Fra2 or FosB caused a repression of promoter activity. The ability of homodimeric JunD/eb1 to elevate TIMP-1 promoter activity supports a role for JunD homodimers as the major AP-1-dependent transactivators of the TIMP-1 gene. IL-6 promoter activity was induced upon activation of HSCs and also required JunD activity; however, expression of JunD/eb1 homodimers resulted in transcriptional repression. Mutagenesis of the IL-6 promoter showed that an AP-1 DNA-binding site previously reported to be an activator of transcription in fibroblasts functions as a suppressor of promoter activity in HSCs. We conclude that JunD activates IL-6 gene transcription as a heterodimer and operates at an alternative DNA-binding site in the promoter. The relevance of these findings to events occurring in the injured liver was addressed by showing that AP-1 DNA-binding complexes are induced during HSC activation and contain JunD as the predominant Jun family protein. JunD is therefore an important transcriptional regulator of genes responsive to Jun homo- and heterodimers in activated HSCs.

* This work was supported by Medical Research Council Component Grant G9900951 (to D. A. M.) and Cooperative Group Grant G9900297 (to D. A. M. and M. J. P. A.), Wellcome Trust Grant 050443/Z (to D. A. M. and M. J. P. A.), and a Wessex Medical Trust Ph.D. studentship (to D. A. M. and D. E. S.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

|| To whom correspondence should be addressed. Tel.: 44-23-80796871; Fax: 44-23-80794154; E-mail: dam2@soton.ac.uk.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Exp. Biol. Med.Home page
F. Jiang and B. Stefanovic
Homeobox Gene Prx1 Is Expressed in Activated Hepatic Stellate Cells and Transactivates Collagen {alpha}1(I) Promoter
Experimental Biology and Medicine, March 1, 2008; 233(3): 286 - 296.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
S. L. Friedman
Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver
Physiol Rev, January 1, 2008; 88(1): 125 - 172.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
S. Lin, N. K. Saxena, X. Ding, L. L. Stein, and F. A. Anania
Leptin Increases Tissue Inhibitor of Metalloproteinase I (TIMP-1) Gene Expression by a Specificity Protein 1/Signal Transducer and Activator of Transcription 3 Mechanism
Mol. Endocrinol., December 1, 2006; 20(12): 3376 - 3388.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
N. Juretic, P. Garcia-Huidobro, J. A. Iturrieta, E. Jaimovich, and N. Riveros
Depolarization-induced slow Ca2+ transients stimulate transcription of IL-6 gene in skeletal muscle cells
Am J Physiol Cell Physiol, May 1, 2006; 290(5): C1428 - C1436.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. Matsuo, S. Tanaka, M. K. Gordon, M. Koch, H. Yoshioka, and F. Ramirez
CREB-AP1 Protein Complexes Regulate Transcription of the Collagen XXIV Gene (Col24a1) in Osteoblasts
J. Biol. Chem., March 3, 2006; 281(9): 5445 - 5452.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. Mann, C. N. Patrick, M. S. Cragg, J. Honeychurch, D. A. Mann, and M. Harris
Functional Analysis of HIV Type 1 Nef Reveals a Role for PAK2 as a Regulator of Cell Phenotype and Function in the Murine Dendritic Cell Line, DC2.4
J. Immunol., November 15, 2005; 175(10): 6560 - 6569.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
D. Hilfiker-Kleiner, A. Hilfiker, K. Kaminski, A. Schaefer, J.-K. Park, K. Michel, A. Quint, M. Yaniv, J. B. Weitzman, and H. Drexler
Lack of JunD Promotes Pressure Overload-Induced Apoptosis, Hypertrophic Growth, and Angiogenesis in the Heart
Circulation, September 6, 2005; 112(10): 1470 - 1477.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. Fiorucci, G. Rizzo, E. Antonelli, B. Renga, A. Mencarelli, L. Riccardi, S. Orlandi, M. Pruzanski, A. Morelli, and R. Pellicciari
A Farnesoid X Receptor-Small Heterodimer Partner Regulatory Cascade Modulates Tissue Metalloproteinase Inhibitor-1 and Matrix Metalloprotease Expression in Hepatic Stellate Cells and Promotes Resolution of Liver Fibrosis
J. Pharmacol. Exp. Ther., August 1, 2005; 314(2): 584 - 595.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Bertrand-Philippe, R. G. Ruddell, M. J. P. Arthur, J. Thomas, N. Mungalsingh, and D. A. Mann
Regulation of Tissue Inhibitor of Metalloproteinase 1 Gene Transcription by RUNX1 and RUNX2
J. Biol. Chem., June 4, 2004; 279(23): 24530 - 24539.
[Abstract] [Full Text] [PDF]

Home page
 J. Histochem. Cytochem.Home page
W. Hipkaeo, T. Wakayama, M. Yamamoto, and S. Iseki
Expression and Localization of the Transcription Factor JunD in the Duct System of Mouse Submandibular Gland
J. Histochem. Cytochem., April 1, 2004; 52(4): 479 - 490.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Hazra, S. Xiong, J. Wang, R. A. Rippe, V. Krishna, K. Chatterjee, and H. Tsukamoto
Peroxisome Proliferator-activated Receptor {gamma} Induces a Phenotypic Switch from Activated to Quiescent Hepatic Stellate Cells
J. Biol. Chem., March 19, 2004; 279(12): 11392 - 11401.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Q. Cao, K. M. Mak, C. Ren, and C. S. Lieber
Leptin Stimulates Tissue Inhibitor of Metalloproteinase-1 in Human Hepatic Stellate Cells: RESPECTIVE ROLES OF THE JAK/STAT AND JAK-MEDIATED H2O2-DEPENDENT MAPK PATHWAYS
J. Biol. Chem., February 6, 2004; 279(6): 4292 - 4304.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
R. A. Frost, G. J. Nystrom, and C. H. Lang
Lipopolysaccharide and proinflammatory cytokines stimulate interleukin-6 expression in C2C12 myoblasts: role of the Jun NH2-terminal kinase
Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2003; 285(5): R1153 - R1164.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M.-C. Hall, D. A. Young, J. G. Waters, A. D. Rowan, A. Chantry, D. R. Edwards, and I. M. Clark
The Comparative Role of Activator Protein 1 and Smad Factors in the Regulation of Timp-1 and MMP-1 Gene Expression by Transforming Growth Factor-beta 1
J. Biol. Chem., March 14, 2003; 278(12): 10304 - 10313.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
C. Huang, J. Li, Q. Zhang, and X. Huang
Role of Bioavailable Iron in Coal Dust-Induced Activation of Activator Protein-1 and Nuclear Factor of Activated T Cells: Difference between Pennsylvania and Utah Coal Dusts
Am. J. Respir. Cell Mol. Biol., November 1, 2002; 27(5): 568 - 574.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
D A Mann and D E Smart
Transcriptional regulation of hepatic stellate cell activation
Gut, June 1, 2002; 50(6): 891 - 896.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Mann, F. Oakley, P. W. M. Johnson, and D. A. Mann
CD40 Induces Interleukin-6 Gene Transcription in Dendritic Cells. REGULATION BY TRAF2, AP-1, NF-kappa B, AND CBF1
J. Biol. Chem., May 3, 2002; 277(19): 17125 - 17138.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.