RESEARCH ARTICLE
Sphingolipid Regulation of Tissue Fibrosis
Barry S Shea , Andrew M Tager*
Article Information
Identifiers and Pagination:
Year: 2012Volume: 6
Issue: Suppl 1
First Page: 123
Last Page: 129
Publisher ID: TORJ-6-123
DOI: 10.2174/1874312901206010123
Article History:
Received Date: 3/3/2012Revision Received Date: 27/3/2012
Acceptance Date: 4/4/2012
Electronic publication date: 15/6/2012
Collection year: 2012
open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
Abstract
Bioactive sphingolipids, such as sphingosine 1-phosphate (S1P), dihydrosphingosine 1-phosphate (dhS1P) and ceramide, regulate a diverse array of cellular processes. Many of these processes are important components of wound-healing responses to tissue injury, including cellular apoptosis, vascular leak, fibroblast migration, and TGF-β signaling. Since over-exuberant or aberrant wound-healing responses to repetitive injury have been implicated in the pathogenesis of tissue fibrosis, these signaling sphingolipids have the potential to influence the development and progression of fibrotic diseases. Here we review accumulating in vitro and in vivo data indicating that these lipid mediators can in fact influence fibrogenesis in numerous organ systems, including the lungs, skin, liver, heart, and eye. Targeting these lipids, their receptors, or the enzymes involved in their metabolism consequently now appears to hold great promise for the development of novel therapies for fibrotic diseases.
