Significance of Adrenergic Nerve Remodeling in Pulmonary Fibrosis
Abstract
Our proposal investigates a specific Fiscal Year 2019 Peer Reviewed Medical Research Program Topic Area of Encouragement: “research into the pathobiology and molecular mechanisms underlying the development of pulmonary fibrosis.” Idiopathic pulmonary fibrosis, known as IPF, is a chronic and progressive form of pneumonia that has no known cause and is highly lethal. Indeed, IPF has a dismal survival of, on average, only 2-3 years after initial diagnosis and is the cause of 40,000 deaths annually in the United States of America alone. Undoubtedly, improved therapies are desperately needed for this disease. A key reason for the lethality of pulmonary fibrosis and the suboptimal treatments is that our understanding of the biological processes underlying this disease are poorly understood. Our studies aim to improve our understanding of the processes that go awry in pulmonary fibrosis and, thus, suggest novel therapeutic strategies to combat this devastating disease. To this end, we have assembled a synergistic team with diverse expertise that have come together with the collective goal of making seminal insights into pulmonary fibrosis. The Principal Investigator has expertise in mouse models of lung disease and fibrosis. One co-investigator is an expert in human pulmonary fibrosis as well as mouse models of this disease. The other co-investigator is a leading non-cancer human lung pathologist and has vast experience in the pathology of lung fibrosis in humans and experimental models, including the mouse. Another colleague provides a letter of support to the team in regard to adrenergic receptor activation. Biological structures are composed of two compartments: the cellular compartment and the extracellular compartment. The extracellular compartment is largely comprised of connective tissue. In lung fibrosis, this extracellular component accumulates excessive amounts of aberrantly stiff connective tissue that markedly impairs the function of the lung, which requires elasticity for each inhalation and exhalation. The nerves of the lung, particularly those that release a hormone called Noradrenaline, appear to be abnormal in the fibrotic lung, and we plan to study if this observation contributes to disease. Our preliminary studies indicate that Noradrenaline producing nerves appear in fibrotic regions. Interruption of Noradrenaline release or activation suppresses fibrosis in laboratory animals, but many questions remain. The main goal of the proposed studies is to understand whether Noradrenaline produced by nerves of the lung is involved the development or progression of scar tissue. To answer this question, we will use tissue samples from patients with IPF and two mouse models of pulmonary fibrosis. If successful, it may be possible to one day use drugs that target this pathway to treat IPF and related diseases.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010157
Entities
People
- Huanxing Sun
Organizations
- United States Army
- Yale University