title: Activation of dermal connective tissue in scleroderma.
abstract: Systemic scleroderma is an acquired disorder which typically results in fibrosis of the skin and internal organs. The pathogenesis of systemic scleroderma is characterized by three distinct processes: microvascular alterations including capillary endothelial cell injury, perivascular inflammatory reaction in dermis, and excessive accumulation of collagen in the dermal layer of lesional skin. In this review, molecular mechanisms resulting in activation of collagen synthesis by dermal fibroblasts in scleroderma are discussed. Specifically, the role of inflammatory cells and the cytokines/growth factors produced by these cells in the pathogenesis of scleroderma is emphasized. The possibilities for prevention and resolution of tissue fibrosis on the basis of these observations are also discussed. Understanding the pathogenetic mechanisms of scleroderma at a molecular level is likely to provide possibilities for development of more specific therapeutic modalities for this and other fibrotic disorders.
authors.affiliation: Department of Dermatology, University of Turku, Finland.
authors.forename: V M
authors.initials: VM
authors.lastname: Kähäri
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D003238:Connective Tissue / Q000378:metabolism; D016572:Cyclosporine / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D006801:Humans; D016023:Integrins / Q000378:metabolism; D007371:Interferon-gamma / Q000627:therapeutic use; D008297:Male; D010396:Penicillamine / Q000627:therapeutic use; D017893:Photopheresis; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors; D012595:Scleroderma, Systemic / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D012744:Sex Ratio; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D016023:Integrins; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D016572:Cyclosporine; D003094:Collagen; D011393:Procollagen-Proline Dioxygenase; D010396:Penicillamine