[Frontiers in Bioscience S1, 226-235, June 1, 2009]

[Frontiers in Bioscience S1, 226-235, June 1, 2009]

Transforming growth factor-beta in systemic sclerosis (scleroderma)

John Varga¹, Michael L. Whitfield²

1Feinberg School of Medicine, Northwestern University, Chicago IL,²Dartmouth Medical School, Hanover, NH

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Fibrosis in SSc
4. Insights from genetic studies
5. Gene expression profiling: 5.1. Insights from gene expression in the skin; 5.2. Studies in fibroblasts; 5.3. Peripheral blood cells and interferon; 5.4. Quantification of heterogeneity at the molecular level; 5.5. Heterogeneity in SSc skin at the pathway level
6. Insights from animal models of SSc
7. Mediators of fibrosis: 7.1. Profibrotic factors: TGF-ß in SSc; 7.2. Other profibrotic mediators; 7.3. Anti-fibrotic mediators
8. Summary and perspectives
9. References

1. ABSTRACT

Deregulated transforming growth factor-beta (TGF-beta) activity and responses play prominent roles in the pathogenesis of systemic sclerosis (SSc), a chronic and progressive connective tissue disease characterized by fibrosis of the skin and internal organs. Systemic sclerosis has highly heterogeneous clinical manifestations, and patients can be classified into multiple subgroups on the basis of distinct molecular signatures defined by transcriptional profiling of gene expression in target organs. Current research to uncover how TGF-beta regulates fibroblast function opens the door for the discovery of targeted therapies. Anti-fibrotic treatments that selectively block TGF-ß expression, biological activity or intracellular signaling in SSc are currently under development.