spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search    

The fully linked HTML version of this article has now been published.
JCS ePress online publication date 18 Sep 2007
doi: 10.1242/jcs.006916

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jcs.006916v1
120/20/3509    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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 Chen, C.-L.
Right arrow Articles by Huang, J. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, C.-L.
Right arrow Articles by Huang, J. S.
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   Add to Twitter  
What's this?

Research Article

Cholesterol suppresses cellular TGF-{beta} responsiveness: implications in atherogenesis


Chun-Lin Chen, I-Hua Liu, Steven J. Fliesler, Xianlin Han, Shuan Shian Huang, and Jung San Huang*
* Author for correspondence (e-mail: huangjs{at}slu.edu)

Hypercholesterolemia is a major causative factor for atherosclerotic cardiovascular disease. The molecular mechanisms by which cholesterol initiates and facilitates the process of atherosclerosis are not well understood. Here, we demonstrate that cholesterol treatment suppresses or attenuates TGF-{beta} responsiveness in all cell types studied as determined by measuring TGF-{beta}-induced Smad2 phosphorylation and nuclear translocation, TGF-{beta}-induced PAI-1 expression, TGF-{beta}-induced luciferase reporter gene expression and TGF-{beta}-induced growth inhibition. Cholesterol, alone or complexed in lipoproteins (LDL, VLDL), suppresses TGF-{beta} responsiveness by increasing lipid raft and/or caveolae accumulation of TGF-{beta} receptors and facilitating rapid degradation of TGF-{beta} and thus suppressing TGF-{beta}-induced signaling. Conversely, cholesterol-lowering agents (fluvastatin and lovastatin) and cholesterol-depleting agents ({beta}-cyclodextrin and nystatin) enhance TGF-{beta} responsiveness by increasing non-lipid raft microdomain accumulation of TGF-{beta} receptors and facilitating TGF-{beta}-induced signaling. Furthermore, the effects of cholesterol on the cultured cells are also found in the aortic endothelium of ApoE-null mice fed a high-cholesterol diet. These results suggest that high cholesterol contributes to atherogenesis, at least in part, by suppressing TGF-{beta} responsiveness in vascular cells.


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   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 Infect. Immun.Home page
S. Banerjee, J. Ghosh, S. Sen, R. Guha, R. Dhar, M. Ghosh, S. Datta, B. Raychaudhury, K. Naskar, A. K. Haldar, et al.
Designing Therapies against Experimental Visceral Leishmaniasis by Modulating the Membrane Fluidity of Antigen-Presenting Cells
Infect. Immun., June 1, 2009; 77(6): 2330 - 2342.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
C.-L. Chen, W.-H. Hou, I-H. Liu, G. Hsiao, S. S. Huang, and J. S. Huang
Inhibitors of clathrin-dependent endocytosis enhance TGF{beta} signaling and responses
J. Cell Sci., June 1, 2009; 122(11): 1863 - 1871.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
C.-L. Chung, J.-R. Sheu, H.-E. Liu, S.-C. Chang, Y.-C. Chou, W.-L. Chen, D.-S. Chou, and G. Hsiao
Dynasore, a Dynamin Inhibitor, Induces PAI-1 Expression in MeT-5A Human Pleural Mesothelial Cells
Am. J. Respir. Cell Mol. Biol., June 1, 2009; 40(6): 692 - 700.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
W. Zuo and Y.-G. Chen
Specific Activation of Mitogen-activated Protein Kinase by Transforming Growth Factor-{beta} Receptors in Lipid Rafts Is Required for Epithelial Cell Plasticity
Mol. Biol. Cell, February 1, 2009; 20(3): 1020 - 1029.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2007