Pulmonary Fibrosis Study Probes Proteins
Dianhua Jiang, MD, PhD
The National Institutes of Health has awarded a four-year, $2.1 million grant to Cedars-Sinai researchers to investigate the role of certain proteins, known as beta-arrestins, in regulating lung inflammation and fibrosis, or scarring. The goal is to determine the feasibility of targeting these proteins with experimental therapies for pulmonary fibrosis, a respiratory disease with no known cure that leads to serious breathing problems.
The American Lung Association estimates that 140,000 Americans have been diagnosed with pulmonary fibrosis, which affects mainly middle-aged and older individuals. The prognosis is poor, with many patients living only three to five years after diagnosis.
The mechanisms that control lung fibrosis remain poorly understood, and as such there is a critical need for deeper exploration, said Dianhua Jiang, MD, PhD, a research scientist at the Cedars-Sinai Women's Guild Lung Institute and the Department of Medicine Pulmonary Division. He is the contact principal investigator for the study.
|Paul W. Noble, MD|
Jiang and his team hypothesize that beta-arrestin proteins are essential to developing lung scarring. In a 2011 study, Jiang and Paul W. Noble, MD, professor and chair of the Department of Medicine and director of the Lung Institute, found that mouse models lacking beta-arrestin genes demonstrated decreased lung fibrosis. In this new study, they aim to expand their understanding of these adaptor proteins.
"Beta-arrestins regulate the fundamental cellular signaling processes that effect inflammation. They are necessary for fibroblasts to destroy lung tissue, leading to irreversible damage. It is important to identify the critical steps in this process, with the hope of finding new drugs that can target fibrosis," said Noble, principal investigator for the new study. The pathological accumulation of fibroblast cells, which manufacture and maintain connective tissues, is associated with pulmonary fibrosis.
The research team will use mouse models to genetically delete beta-arrestin genes in specific cell types in the lung. They will also test the feasibility of blocking beta-arrestin signaling with RNA inhibitors in mouse models of pulmonary fibrosis.
"Deeper examination of the role of beta-arrestins can potentially lead us to better understanding of the disease and perhaps new avenues of treatment," said Jiang.