An earlier paper Noble published in March in Science Translational Medicine showed that intracellular signaling proteins called beta-arrestins were necessary for fibroblasts to invade tissue. Mice with a targeted deletion in beta-arrestins didn't develop severe pulmonary fibrosis. He did this work with receptor-science pioneer Robert Lefkowitz, M.D., of Duke Departments of Medicine and Biochemistry.
The two studies, taken together, suggest several approaches to treating invasive fibrosis in the lungs, Noble said. They might specifically block hyaluronan production and the receptor for the sugar. Or they might block the invasion process by targeting beta-arrestins to prevent myofibroblasts from making contact with the matrix (noncellular part) of the lung.
Noble thinks looking at additional targets to block the invasion process might be the best approach of all. "If we can study human fibroblasts and also the transgenic mouse as a model system, we could find more clues to stop the cells from invading," he said. "Several drugs are already approved that may have these properties that we need."
|Contact: Mary Jane Gore|
Duke University Medical Center