title: Regulation of matrix biosynthesis and degradation in systemic sclerosis.
abstract: The regulation of matrix biosynthesis in systemic sclerosis has been the focus of many studies, because excessive matrix synthesis causes pathologic changes, and because this would seem to be a good target for therapies aimed at ameliorating the disease. Possible targets for antifibrotic therapies include both matrix gene stimulatory and inhibitory pathways. Much recent progress has been made in understanding the mechanism of action of transforming growth factor-beta (TGF-beta), an important profibrotic cytokine with pleiotropic effects on fibroblasts. It appears that TGF-beta may use multiple signal transduction pathways in fibroblasts and it is possible that defects in any of these pathways may result in an abnormal response to TGF-beta, resulting in fibrosis. Studies on negative regulation of matrix gene expression have singled out the antifibrotic cytokines tumor necrosis factor-alpha and interferon-gamma. Finally, a new approach that compares mRNA expression in normal versus diseased fibroblasts has already lead to the discovery of genes that may play a role in the development of fibrosis. This represents an important advance because genes can be identified that have not previously been implicated in the control of matrix synthesis, and thus might not otherwise have been studied in this context.
authors.affiliation: Boston University School of Medicine, Arthritis Center, Massachusetts 02118, USA. rwidom@medicine.bu.edu
authors.forename: R L
authors.initials: RL
authors.lastname: Widom
mesh_terms: D055513:Connective Tissue Growth Factor; D019175:DNA Methylation; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: C526317:CCN2 protein, human; D016326:Extracellular Matrix Proteins; D006133:Growth Substances; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D055513:Connective Tissue Growth Factor