Cellular and molecular mechanisms of bleomycin-induced murine scleroderma: current update and future perspective.
Scleroderma is a fibrotic condition characterized by immunologic abnormalities, vascular injury and increased accumulation of matrix proteins in the skin. Although the aetiology of scleroderma is not fully elucidated, a growing body of evidence suggests that extracellular matrix overproduction by activated fibroblasts results from complex interactions among endothelial cells, lymphocytes, macrophages and fibroblasts, via a number of mediators. Cytokines, chemokines and growth factors secreted by inflammatory cells and mesenchymal cells (fibroblasts and myofibroblasts) play an important role in the fibrotic process of scleroderma. Recently, we established a murine model of scleroderma by repeated local injections of bleomycin. Dermal sclerosis was induced in various mouse strains, although the intensity of dermal sclerosis varied among various strains. Histopathological and biochemical analysis demonstrated that this experimental murine scleroderma reflected a number of aspects of human scleroderma. Further investigation of the cellular and molecular mechanisms of inflammatory reaction, fibroblast activation and extracellular matrix deposition following dermal injury by bleomycin treatment will lead to the better understanding of the pathophysiology and the exploration of effective treatment against scleroderma. This review summarizes recent progress of the cellular and molecular events in the pathogenesis of bleomycin-induced scleroderma; moreover, further perspective by using this mouse model has been discussed.
Yamamoto
Toshiyuki
T
Department of Dermatology, Tokyo Medical and Dental University, School of Medicine, Tokyo, Japan. yamamoto.derm@med.tmd.ac.jp
Nishioka
Kiyoshi
K
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology*; D002448:Cell Adhesion; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004804:Eosinophils / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D008264:Macrophages / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D018384:Oxidative Stress; D012595:Scleroderma, Systemic / Q000139:chemically induced*; D012867:Skin / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism
D018925:Chemokines; D016207:Cytokines; D001761:Bleomycin