Navigate Up
UPMC/University of Pittsburgh Schools of the Health Sciences
For Journalists
Senior Manager
Telephone: 412-578-9193 or 412-624-3212
Manager
Telephone: 412-586-9762
Other Inquiries

Pitt Researchers Identify Agent That Can Block Fibrosis of Skin, Lungs

PITTSBURGH, May 30 – Researchers at the University of Pittsburgh School of Medicine have identified an agent that in lab tests protected the skin and lungs from fibrosis, a process that can ultimately end in organ failure and even death because the damaged tissue becomes scarred and can no longer function properly. The findings were published today in Science Translational Medicine.

There are no effective therapies for life-threatening illnesses such as idiopathic pulmonary fibrosis and systemic sclerosis, which cause progressive organ scarring and failure, said senior author Carol A. Feghali-Bostwick, Ph.D., associate professor, Division of Pulmonary, Allergy and Critical Care Medicine, and co-Director of the Scleroderma Center, Pitt School of Medicine.

“It’s estimated that tissue fibrosis contributes to 45 percent of all deaths in developed countries because organ failure is the final common pathway for numerous diseases,” she said. “Identifying a way to stop this process from happening could have enormous impact on mortality and quality of life.”

The research team evaluated E4, a piece of protein or peptide derived from endostatin, a component of collagen known for its inhibition of new blood vessel growth. In lab tests, healthy human skin cells that were treated to become fibrotic remained normal when E4 was present. The skin and lungs of mice were protected from cell death and tissue scarring by a single injection of E4 administered five or eight days after they were given the cancer drug bleomycin, which is known to induce fibrosis. The peptide also could reverse scarring that had already occurred, the researchers found.

In a unique approach, the investigators also tested E4 in human skin maintained in the laboratory to confirm it would be effective in treating fibrosis in a human tissue. E4 blocked new and ongoing fibrosis in human skin.

The agent might work by stalling the cross-linking of collagen needed to form thick scars, Dr. Feghali-Bostwick said. While the body naturally produces endostatin, it appears that it cannot make sufficient amounts to counteract fibrosis development in some diseases.
“This endostatin peptide passes two important hurdles that suggest it is a promising candidate drug for development for patients with idiopathic pulmonary fibrosis and systemic sclerosis” said Mark T. Gladwin, M.D., chief, Division of Pulmonary, Allergy and Critical Care Medicine at UPMC and Pitt. “It reverses established disease in animal models and it reverses fibrosis in the human skin fibrosis model.”

In a case of serendipity, the researchers discovered E4 while exploring the process of fibrosis. Post-doctoral fellow and study co-author Yukie Yamaguchi, M.D., Ph.D., was conducting some experiments with proteins thought to facilitate the scarring process.
“Dr. Yamaguchi showed me the tests that showed endostatin wasn’t working to increase fibrosis, but in fact shut it down,” Dr. Feghali-Bostwick said. “It was the opposite of what we expected and I was very excited about our finding. As Louis Pasteur once said, ‘chance favors the prepared mind.’”

Other co-authors include Takahisa Takihara, M.D., Roger A. Chambers, B.S., and Kristen L. Veraldi, M.D., Ph.D., of the Division of Pulmonary, Allergy and Critical Care Medicine, the Department of Pathology, and the Scleroderma Center, Pitt School of Medicine; and Adriana T. Larregina, M.D., Ph.D., of the Departments of Dermatology and Immunology, Pitt School of Medicine, and the McGowan Institute for Regenerative Medicine.

The project was funded by National Institutes of Health grant AR050840.

©  UPMC | Affiliated with the University of Pittsburgh Schools of the Health Sciences
Supplemental content provided by A.D.A.M. Health Solutions. All rights reserved.

For help in finding a doctor or health service that suits your needs, call the UPMC Referral Service at 412-647-UPMC (8762) or 1-800-533-UPMC (8762). Select option 1.

UPMC is an equal opportunity employer. UPMC policy prohibits discrimination or harassment on the basis of race, color, religion, ancestry, national origin, age, sex, genetics, sexual orientation, marital status, familial status, disability, veteran status, or any other legally protected group status. Further, UPMC will continue to support and promote equal employment opportunity, human dignity, and racial, ethnic, and cultural diversity. This policy applies to admissions, employment, and access to and treatment in UPMC programs and activities. This commitment is made by UPMC in accordance with federal, state, and/or local laws and regulations.

Medical information made available on UPMC.com is not intended to be used as a substitute for professional medical advice, diagnosis, or treatment. You should not rely entirely on this information for your health care needs. Ask your own doctor or health care provider any specific medical questions that you have. Further, UPMC.com is not a tool to be used in the case of an emergency. If an emergency arises, you should seek appropriate emergency medical services.

For UPMC Mercy Patients: As a Catholic hospital, UPMC Mercy abides by the Ethical and Religious Directives for Catholic Health Care Services, as determined by the United States Conference of Catholic Bishops. As such, UPMC Mercy neither endorses nor provides medical practices and/or procedures that contradict the moral teachings of the Roman Catholic Church.

© UPMC
Pittsburgh, PA, USA UPMC.com