Fibrosis in connective tissue disease the role of the myofibroblast and fibroblast-epithelial cell interactions.docVIP

Available online /content/9/S2/S4 Review Fibrosis in connective tissue disease: the role of the myofibroblast and fibroblast-epithelial cell interactions Thomas Krieg1, David Abraham2 and Robert Lafyatis3 1Department of Dermatology, University of K?ln, Kerpener Strasse, D-50924 K?ln, Germany 2Department of Medicine, Centre for Rheumatology and Connective Tissue Diseases, Royal Free and University College, Rowland Hill Street, London, NW3 2PF, UK 3Rheumatology Department, Boston University of Medicine, Albany Street, Boston, Massachusetts 02118-2394, USA Corresponding author: Thomas Krieg, thomas.krieg@uni-koeln.de Published: 15 August 2007 Arthritis Research Therapy 2007, 9(Suppl 2):S4 (doi:10.1186/ar2188) This article is online at /content/9/S2/S4 ? 2007 BioMed Central Ltd Abstract cellular and molecular events associated with the initiation and maintenance of fibrosis in CTDs. Fibrosis, characterized by excessive extracellular matrix accumu- lation, is a common feature of many connective tissue diseases, notably scleroderma (systemic sclerosis). Experimental studies suggest that a complex network of intercellular interactions involving endothelial cells, epithelial cells, fibroblasts and immune cells, using an array of molecular mediators, drives the pathogenic events that lead to fibrosis. Transforming growth factor-β and endothelin-1, which are part of a cytokine hierarchy with connec- tive tissue growth factor, are key mediators of fibrogenesis and are primarily responsible for the differentiation of fibroblasts toward a myofibroblast phenotype. The tight skin mouse (Tsk-1) model of cutaneous fibrosis suggests that numerous other genes may also be important. Initiators of fibrosis in connective tissue diseases Fibrosis arises from excessive collagen synthesis by fibroblasts [3]. Of the many potential mediators of fibrosis in CTDs, three molecular entities appear to