Cadherin-11 Regulation of Fibrosis through Modulation of Epithelial-to-Mesenchymal Transition: Implications for Pulmonary Fibrosis in Scleroderma.

摘要

Lung fibrosis is the leading cause of death in scleroderma. Treatment options are limited, stressing the unmet need to advance of understanding of the. We have demonstrated that cadherin-11 (Cad11) is increased in fibrotic skin and lung tissues and that Cad11 is a mediator of fibrosis in mouse models. Mechanistically how this occurs is not known, but our preliminary data point to a role for Cad11 in the regulation of epithelial to mesenchymal transition. In year 1 of the grant, we have performed experiments in the intraperitoneal model of pulmonary fibrosis in wild type and Cad11 deficient mice that show that Cad11 deficient mice have less lung fibrosis. Initial studies studies also suggest that antiCad11 antibodies are effective in treating lung fibrosis in this model. In vitro studies have demonstrated that Cad11 regulates epithelial-to-mesenchymal-transition (EMT) in MLE-12 cells, a mouse alveolar epithelial cell line. These data are confirming our original hypothesis that Cad11 regulates lung fibrosis through modulation of EMT. Finally, in year 1, we identified the patient sera that will be used in year 2 to determine soluble circulating levels of Cad11.