Identification of cadherin 11 as a mediator of dermal fibrosis and possible role in systemic sclerosis.

摘要: Objective Systemic sclerosis (SSc) is a chronic autoimmune disease clinically manifesting as progressive fibrosis of the skin and internal organs. Recent microarray studies demonstrated that cadherin 11 (Cad-11) expression increased in affected patients with SSc. The purpose this study was to examine our hypothesis Cad-11 mediator dermal fibrosis. Methods Biopsy samples from SSc healthy control subjects were used for real-time quantitative polymerase chain reaction analysis assess immunohistochemistry determine pattern Cad-11. To whether fibrosis, Cad-11–deficient mice anti–Cad-11 monoclonal antibodies (mAb) bleomycin-induced model. In vitro fibroblasts bone marrow–derived macrophages mechanisms by which contributes development tissue fibrosis. Results Levels messenger RNA biopsy correlated modified Rodnan thickness scores. localized skin. Cad-11–knockout injected bleomycin had markedly attenuated quantified measurements thickness, collagen levels, myofibroblast accumulation, profibrotic gene expression, lesional compared wild-type mice. addition, mAb decreased at various time points regulated production transforming growth factor β (TGFβ) migration fibroblasts. Conclusion These data demonstrate TGFβ suggest may be therapeutic target