Skip Navigation


Cardiovascular Research Advance Access first published online on February 19, 2009
This version [Corrected Proof] published online on March 19, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp056
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
82/2/303    most recent
cvp056v2
cvp056v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
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 Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Gellings Lowe, N.
Right arrow Articles by Sabbadini, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gellings Lowe, N.
Right arrow Articles by Sabbadini, R. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

Sphingosine-1-phosphate and sphingosine kinase are critical for transforming growth factor-β-stimulated collagen production by cardiac fibroblasts

Nicole Gellings Lowe1, James S. Swaney1,2, Kelli M. Moreno2 and Roger A. Sabbadini1,2,*

1 Department of Biology, San Diego State University, 5500 Campanile Dr, San Diego, CA 92182-4614, USA
2 Lpath Inc., San Diego, CA, USA

* Corresponding author. Tel: +1 858 678 0800 ext 109; fax: +1 858 678 0900. E-mail address: rsabbadini{at}lpath.com

Aims: Following injury, fibroblasts transform into myofibroblasts and produce extracellular matrix (ECM). Excess production of ECM associated with cardiac fibrosis severely inhibits cardiac function. Sphingosine-1-phosphate (S1P), a bioactive lysophospholipid, regulates the function of numerous cell types. In this study, we determined the role of S1P in promoting pro-fibrotic actions of cardiac fibroblasts (CFs).

Methods and results: S1P-mediated effects on myofibroblast transformation, collagen production, and cross-talk with transforming growth factor-β (TGF-β) using mouse CF were examined. S1P increased {alpha}-smooth muscle actin (a myofibroblast marker) and collagen expression in a S1P2 receptor- and Rho kinase-dependent manner. TGF-β increased sphingosine kinase 1 (SphK1; the enzyme responsible for S1P production) expression and activity. TGF-β-stimulated collagen production was inhibited by SphK1 or S1P2 siRNA, a SphK inhibitor, and an anti-S1P monoclonal antibody.

Conclusion: These findings suggest that TGF-β-stimulated collagen production in CF involves ‘inside-out’ S1P signalling whereby S1P produced intracellularly by SphK1 can be released and act in an autocrine/paracrine fashion to activate S1P2 and increase collagen production.

KEYWORDS {alpha}-Smooth muscle actin; Cardiac fibroblast; Collagen; Fibrosis; S1P; Sphingosine kinase; TGF-β

Time for primary review: 24 days


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Am. J. Physiol. Cell Physiol.Home page
J. Igarashi, K. Shoji, T. Hashimoto, T. Moriue, K. Yoneda, T. Takamura, T. Yamashita, Y. Kubota, and H. Kosaka
Transforming growth factor-{beta}1 downregulates caveolin-1 expression and enhances sphingosine 1-phosphate signaling in cultured vascular endothelial cells
Am J Physiol Cell Physiol, November 1, 2009; 297(5): C1263 - C1274.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
C. K. Means and J. H. Brown
Sphingosine-1-phosphate receptor signalling in the heart
Cardiovasc Res, May 1, 2009; 82(2): 193 - 200.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
J. S. Karliner and J. H. Brown
Lipid signalling in cardiovascular pathophysiology
Cardiovasc Res, May 1, 2009; 82(2): 171 - 174.
[Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.