Cadherin-11 Regulation of Fibrosis through Modulation of Epithelial-to-Mesenchymal Transition: Implications for Pulmonary Fibrosis in Scleroderma
Technical Report,30 Sep 2014,29 Sep 2015
Baylor College of Medicine Houston United States
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Systemic sclerosis is a potentially devastating multisystem disorder characterized inflammation and autoimmunity, vasculopathy, and excessive extracellular matrix deposition. Treatment options are limited, nontargeted, potentiallytoxic and minimally effective, stressing the unmet need to advance of understanding of the pathogenesis with the hope of identifying novel therapeutic targets. Cadherin-11 is a type II mesenchymal cadherin. More recently, we have identified the expression of cadherin-11 on dermal and lung fibroblasts and its further upregulation by TGFbeta,a key cytokine in scleroderma pathogenesis. Herein we propose to investigate the role of cadherin-11 inmodulating epithelial to mesenchymal transition of alveolar epithelial cells using both in vivo and in vitro approaches. Finally we will use a prospective cohort of scleroderma patients to determine if plasma levels of cadherin-11 levels are elevated in patients with interstitial lung disease and if these levels correlate with lung function.