Abstract
ObjectiveSystemic sclerosis (SSc) is an autoimmune disease clinically manifesting as progressive fibrosis of the skin and internal organs. Cadherin-11 (CDH11) expression is increased in fibrotic skin and lung tissue. Targeting CDH11 may be an effective approach to treating fibrosis. We hypothesize that targeting CDH11 will decrease fibrosis in the tight skin-1 (Tsk-1) mouse model.MethodsCDH11 expression was determined in the Tsk-1 mouse model using quantitative real time PCR and immunofluorescence (IF). Inhibitory anti- CDH11 monoclonal antibodies were tested in Tsk-1 mice for their ability to decrease hypodermal fibrosis.ResultsExpression of CDH11 was increased in fibrotic skin from Tsk-1 mice compared to pallid controls. IF staining demonstrated that CDH11 expression localized to fibroblasts within the hypodermis of fibrotic skin. Treatment with inhibitory anti-CDH11 monoclonal antibodies decreased hypodermal thickness and fibrotic mediators in Tsk-1 mice compared to control antibodies.ConclusionsThese data demonstrate an important role for CDH11 in the development of skin fibrosis in Tsk-1 mice. These data add to the growing evidence for the important role of CDH11 in tissue fibrosis and fibrotic disease such as systemic sclerosis.
Highlights
Scleroderma is an autoimmune disease clinically characterized by progressive fibrosis of the skin and internal organs
Treatment with inhibitory anti-CDH11 monoclonal antibodies decreased hypodermal thickness and fibrotic mediators in tight skin-1 (Tsk-1) mice compared to control antibodies. These data demonstrate an important role for CDH11 in the development of skin fibrosis in Tsk-1 mice
These data add to the growing evidence for the important role of CDH11 in tissue fibrosis and fibrotic disease such as systemic sclerosis
Summary
Systemic sclerosis (SSc) is an autoimmune disease clinically manifesting as progressive fibrosis of the skin and internal organs. Cadherin-11 (CDH11) expression is increased in fibrotic skin and lung tissue. Targeting CDH11 may be an effective approach to treating fibrosis. We hypothesize that targeting CDH11 will decrease fibrosis in the tight skin-1 (Tsk1) mouse model
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