Study Led by Feghali-Bostwick Finds Potential Target for Fibrosis Treatment

Issue Date: 
October 4, 2010

Researchers in the University of Pittsburgh School of Medicine have discovered that a molecule that regulates gene expression plays a central role in the development of fibrosis, a condition in which organ-supporting connective tissues become thick, hard, and rigid, restricting normal function. The findings are available in the American Journal of Pathology.

Early Growth Receptor-1 (EGR-1) orchestrates the response to certain growth factors and influences the activity of numerous genes, said Carol Feghali-Bostwick, principal investigator and a professor of medicine and pathology in the University of Pittsburgh School of Medicine.

“Our study shows that abnormally high levels of EGR-1 are associated with the development of fibrosis,” Feghali-Bostwick said. “Therefore, controlling EGR-1 could be a potential therapy for disorders such as scleroderma and pulmonary fibrosis.”

Researchers induced fibrosis in animal and human fibroblasts, which are cells that give rise to connective tissue by utilizing a secreted protein called IGFBP-5 (insulin-like growth factor binding protein 5), made by a gene that is overexpressed in fibrotic lung and skin tissues. They found that the experimentally induced fibrosis was associated with abnormally elevated EGR-1 activity. More importantly, when fibrosis was produced in cells and animals lacking EGR-1, the amount of fibrosis was dramatically reduced.

“We also found that compared to healthy individuals, people who have pulmonary fibrosis had higher levels of EGR-1 in samples of their lung tissue and in their fibroblasts,” Feghali-Bostwick said. The findings suggest that targeting EGR-1 provides a potential therapeutic approach for organ fibrosis.

Researchers received funding for the study from the National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Heart, Lung, and Blood Institute; the American Lung Association; the American Heart Association Pennsylvania/Delaware affiliate; and the Uehara Memorial Foundation.