Animal models of systemic sclerosis: insights into systemic sclerosis pathogenesis and potential therapeutic approaches.
OBJECTIVE
Animal models have been extremely valuable in contributing to a better understanding of the pathogenesis of systemic sclerosis. Discussed here are recent studies that have examined the molecular pathways and potential therapeutic approaches for systemic sclerosis using animal models.


RESULTS
Reported evidence further indicates that the immune system plays a role in modulating the fibrosis observed in the tight skin-1/+ mouse model for systemic sclerosis. CD19, interleukin-6, and interleukin-4 are involved. The injection of spleen cells into immune-compromised mice resulted in fibrotic, vascular, and immunologic alterations quite similar to those of systemic sclerosis. Transforming growth factor-beta and its signaling pathway (JAK kinase and STAT-6, Smad2/3, and Smad7) appear to play a central role in the development of fibrosis as well as monocyte chemoattractant protein-1, CCR-2, platelet-derived growth factor C, and excessive apoptosis. Viruses were shown to be possible cofactors. The therapeutic agents hepatocyte growth factor and halofuginone were shown to prevent fibrosis in animal models of systemic sclerosis.


CONCLUSIONS
The transforming growth factor-beta signaling pathway is a common mechanism of tissue fibrosis in animal models of systemic sclerosis, although numerous additional molecules modulate this pathway or have a direct effect on fibrosis.
Christner
Paul J
PJ
Division of Rheumatology, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, USA.
Jimenez
Sergio A
SA
D000818:Animals; D004195:Disease Models, Animal; D051379:Mice; D018345:Mice, Knockout; D012595:Scleroderma, Systemic / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy*