University of Pittsburgh Scientists Find Potential Target for Fibrosis Treatment
PITTSBURGH, April 27, 2010 – Researchers at 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 April edition of 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, Ph.D., principal investigator and associate professor of medicine and pathology at the University of Pittsburgh School of Medicine.
“Our study shows that abnormally high levels of EGR-1 are associated with the development of fibrosis,” Dr. 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,” Dr. Feghali-Bostwick noted. The findings suggest that targeting EGR-1 provides a potential therapeutic approach for organ fibrosis.
Hidekata Yasuoka, Eileen Hsu, Ximena D. Ruiz and Richard A. Steinman, all from the University of Pittsburgh; and Augustine M.K. Choi from Brigham and Women’s Hospital, co-authored the paper.
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.
About the University of Pittsburgh School of Medicine
As one of the nation’s leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1997 and now ranks fifth in the nation, according to preliminary data for fiscal year 2008. Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region’s economy. For more information about the School of Medicine, see www.medschool.pitt.edu.