The bleomycin-induced scleroderma model: what have we learned for scleroderma pathogenesis?
Scleroderma is a fibrotic condition characterized by immunologic abnormalities, vascular injury and increased accumulation of extracellular matrix (ECM) proteins in the skin. Although the etiology of scleroderma has not yet been fully elucidated, a growing body of evidence suggests that ECM overproduction by activated fibroblasts results from complex interactions among endothelial cells, lymphocytes, macrophages and fibroblasts, via a number of mediators, such as cytokines, chemokines and growth factors. For a better understanding of the pathophysiology of scleroderma, animal models are important tools. We established a murine model of cutaneous sclerosis by local treatment of bleomycin. This model reproduces several histological as well as biochemical aspects of human scleroderma. However, it must be emphasized that studying animal models cannot answer all the problems of human scleroderma. In this review, we introduce current insights into the pathogenesis of bleomycin-induced scleroderma, and discuss its contribution to our understanding of the pathogenesis of, and treatments for, human scleroderma.
Yamamoto
Toshiyuki
T
Department of Dermatology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, 160-0023 Tokyo, Japan. toyamade@tokyo-med.ac.jp
D000818:Animals; D017209:Apoptosis; D001761:Bleomycin; D018925:Chemokines / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D005347:Fibroblasts / Q000473:pathology / Q000502:physiology; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D008214:Lymphocytes / Q000473:pathology / Q000502:physiology; D008264:Macrophages / Q000473:pathology / Q000502:physiology; D051379:Mice; D018384:Oxidative Stress; D012595:Scleroderma, Systemic / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D015398:Signal Transduction
D018925:Chemokines; D016207:Cytokines; D006133:Growth Substances; D001761:Bleomycin