Animal model of systemic sclerosis

Abstract

Scleroderma is a fibrotic condition characterized by immunological abnormalities, vascular injury and increased accumulation of extracellular matrix proteins in the skin. Although the etiology of scleroderma has not yet been fully elucidated, a growing body of evidence suggests that extracellular matrix overproduction by activated fibroblasts results from a complex interaction among endothelial cells, lymphocytes, macrophages and fibroblasts, through 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. These models reproduce several histological as well as biochemical aspects of human scleroderma, and we can learn a lot through animal studies. On the other hand, it must be emphasized that studying animal models cannot answer all the problems of human scleroderma. In this review, I introduce current insights into the pathogenesis and also recent updates of therapeutic approaches using several animal models of SSc, and discuss their contribution to our understanding of the pathogenesis of, and treatments for, human scleroderma.

Traditional Japanese formulas tokishakuyakusan and ogikenchuto suppress dermal sclerosis in bleomycin‐induced murine scleroderma

“…inhibition of TGF-β [24]. In this study, TGF-β1 expression had been suppressed by all the kampo formulas 1 week after BLM injection.…”

“…Specific pathogen-free, 6-week-old, female C3H/HeJ YOK mice were purchased from Japan SLC (Shizuoka, Japan) and housed in a controlled environment (23)(24)(25) C; 12 h light/ dark cycle). The C3H/HeJ mouse strain is considered a suitable experimental model of BLM-induced scleroderma [12].…”

Double heterozygous mice for Klf5 and Fli1 genes: a new animal model of systemic sclerosis recapitulating its three cardinal pathological features

“…The extensive studies on the pathological processes of these models provide increasing insights into the fibrotic and, to a lesser extent, immunological aspects of SSc. These inducible models are quite useful because they are easily applicable to mice with genetic mutations, elucidating the potential roles of various molecules and signaling pathways in SSc [3,8]. Also, the preventive and curative effects of drugs on tissue fibrosis are capable to be examined in these models.…”

“…The most widely used and established ones among inducible models include a bleomycin-treated SSc murine model and a sclerodermatous graft-versus-host disease model [3,4]. Furthermore, during the recent several years, three new inducible animal models of SSc have been established utilizing reactive oxygen species [5], anti-DNA topoisomerase I antibody [6] and angiotensin II [7].…”

Scleroderma Renal Crisis

“…One of the better-known models is bleomycin-induced scleroderma. A repeated intradermal or subcutaneous injection of bleomycin into rats and mice leads to the development of dermal sclerosis (Mountz et al, 1983;Yamamoto;Yamamoto & Nishioka, 2001Yamamoto, Takahashi, Takagawa, Katayama, & Nishioka, 1999). The latter is microscopically characterized by the deposition of thick collagen bundles, homogeneous acellular material, and cellular infiltrates of T-cells, macrophages, and mast cells.…”