The Role of Exosomes on the Alveolar Epithelium in Idiopathic Pulmonary Fibrosis
Abstract
Our application aligns with the goal of the Fiscal Year 2022 Peer Reviewed Medical Research Program and addresses the Pulmonary Fibrosis Topic Area. Also, we focus on a Strategic Goal: Develop and test novel treatments, including precision medicine approaches, to slow the progression or reverse lung injury/disease. Studies have demonstrated that chronic lung diseases are more common among deployed veterans than non-deployed Veterans. Veterans were exposed to a very harsh and specific environment during their deployment. Inhalation of harmful chemicals and particles can induce respiratory problems and lung injury leading to several pulmonary diseases. Idiopathic pulmonary fibrosis (IPF) is the most common and progressive fibrotic lung disease, with a 5-year mortality rate of 50%-70%. The pathophysiology of this disease is not well known. The thickened and stiff tissue makes it difficult for the patient lungs to work properly. Although there is an urgent need to develop an effective treatment for IPF, successful therapy is currently not available due to the lack of novel approaches. Lung transplantation remains the primary intervention to improve survival; however, it is linked to increased morbidity and mortality risks. A better understanding, novel targets, and effective therapies are needed. The particles inhaled by Veterans were deposited in the lungs and not eliminated completely. Their persistence induces chronic respiratory diseases. Injured lung cells secrete exosomes, small membrane vesicles, to their microenvironment. Their content can dramatically change under pathological conditions. Therefore, most exosomes secreted from diseased cells induce inflammation, spread damage, and alter the phenotype of various neighboring cells. Exosomes can deliver harmful contents to different organs, including the lung, leading to their failure. We will isolate exosomes from lung transplants of IPF patients in the current project. The harmful impact of exosomes will be determined on alveolar cells obtained from control organ donors whose lungs were not suitable for transplantation and were donated for medical research. Alveolar cells have stem cell potential in the adult lung. We will study fatty acid synthesis enzymes, which are critical for alveolar cell function, and whose impairment can lead to susceptibility and worseness of IPF. Targeting harmful exosome loads can be used as a novel approach to developing novel methods to diagnose IPF accurately. It can also lead to therapeutic strategies to minimize IPF and inhibit exosomes’ spreading and disease progression. There is no commercial pharmaceutical drug to target harmful exosomes; therefore, we will also focus on the therapeutic function of RNA factors. They have proven their effectiveness in fighting several diseases, including pulmonary abnormalities, especially when conventional therapy fails. We will block the exosomes with harmful content as a novel potential therapeutic strategy. This approach can lead to novel treatments to prevent IPF development. There is an urgent need to develop novel treatments for IPF that interrupt this destructive cycle and restore the normal lung milieu to improve the outcomes and achieve the ultimate goal of curing patients with this disease. Our study has clinical implications and can identify novel therapeutic targets. Our short-term goal is to identify the harmful effect of exosomes obtained from IPF patients on control alveolar cells obtained from organ donors. Identifying dysregulated proteins by exosomes can lead to discovering novel IPF biomarkers and therapeutic targets. Our long-term goal is to develop a new class of medications that block harmful exosome load, which can stimulate lung regeneration after injury.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310368
Entities
People
- Karim Bahmed
Organizations
- Temple University
- United States Army