Sphingolipid Regulation of Tissue Fibrosis



Barry S Shea , Andrew M Tager*
Pulmonary and Critical Care Unit, and Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA 02114, USA


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© Shea and Tager; Licensee Bentham Open.

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.

* Address correspondence to this author at the Pulmonary and Critical Care Unit, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, 149 13th Street, Room 8301, Charlestown, MA 02129, USA; Tel: (617) 724-7368; Fax: (617) 726-5651; E-mail: amtager@partners.org


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.

Keywords: Fibrosis, sphingolipids, S1P..