title: Critical Appraisal of the Utility and Limitations of Animal Models of Scleroderma.
abstract: Scleroderma, also called systemic sclerosis (SSc), is an autoimmune connective tissue disease characterized by abnormality of the immune system, cardiovascular disorder, and fibrosis of the skin, lung, kidney, and other internal organs. Skin symptom and stiffness of the skin with accumulation of collagen cause severe disability, and cardiovascular and lung complications lead to high mortality. Despite recent progress, therapies for these complications in SSc are limited and the underlying mechanisms are poorly understood. Animal models are one strategy to identify molecular mechanisms and pathways underlying these complications of SSc and could provide a mechanistic basis for a design of clinical trials. However, although several animal models have been reported to reproduce some aspects of SSc, none of them recapitulates all of the pathological features of SSc. In this review, we describe previously reported animal models of scleroderma and discuss their utility and limitations in efforts to understand the mechanisms underlying scleroderma and develop new treatments for this disease.
authors.affiliation: Department of Medicine, University of California, San Francisco, CA, 94143, USA. kazuyuki.tsujino@ucsf.edu.|Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. kazuyuki.tsujino@ucsf.edu.|Department of Medicine, Lung Biology Center, University of California, San Francisco, Box 2922, San Francisco, CA, 94143-2922, USA. kazuyuki.tsujino@ucsf.edu.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tsujino
authors.affiliation: Department of Medicine, University of California, San Francisco, CA, 94143, USA. dean.sheppard@ucsf.edu.|Department of Medicine, Lung Biology Center, University of California, San Francisco, Box 2922, San Francisco, CA, 94143-2922, USA. dean.sheppard@ucsf.edu.
authors.forename: Dean
authors.initials: D
authors.lastname: Sheppard
mesh_terms: D000804:Angiotensin II; D000818:Animals; D001761:Bleomycin; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006086:Graft vs Host Disease / Q000150:complications; D051379:Mice; D008822:Mice, Transgenic; D017382:Reactive Oxygen Species; D012595:Scleroderma, Systemic / Q000209:etiology*
chemical_list: D017382:Reactive Oxygen Species; D001761:Bleomycin; D000804:Angiotensin II
keywords: Animal models; Autoimmunity; Fibrosis; Inflammation; Systemic sclerosis; Vasculopathy