Activated fibroblasts are the key mediators of fibrosis and these cells are derived from both resident cells as well as from circulating cells termed fibrocytes. Fibrocytes are known to contribute significantly to the total population of fibroblasts in a variety of progressive fibrotic diseases including idiopathic pulmonary fibrosis (IPF), a progressive and fatal form of lung disease for which there are no effective or specific treatments. Others have utilized direct counting of fibrocytes to identify inhibitors of fibrocyte differentiation that reduce the development of fibrosis in animal models, however this method is not amenable to high-throughput drug screening. We have developed a simple and reliable method to quantify fibrocytes that can be used to identify drugs targeting fibrocyte development and differentiation and we demonstrate that this makes small molecule drug discovery efforts against this pathophysiologic target possible. The goal of this Phase I project is to show that our method can be used for high-throughput drug screening (HTS). The ability to undertake HTS will allow us to identify of a new class of specific antifibrotic drugs to treat IPF and related diseases during Phase II. These drugs will serve an unmet clinical need and could reduce the morbidity and mortality associated with fibrotic illnesses and lead to improvements in Public Health. In addition, these compounds may serve as useful biological probes of fibrocyte function.
Public Health Relevance: Fibrocytes are a type of blood cells that are involved in a variety of progressive fibrotic diseases including idiopathic pulmonary fibrosis (IPF), a fatal form of lung disease for which there are no effective or specific treatments. This application aims to demonstrate that the methods that we have developed will allow for high throughput screening (HTS). The ability to undertake HTS will allow for the discovery of drugs targeting fibrocytes. These drugs will serve an unmet clinical need and could reduce the morbidity and mortality associated with fibrotic illnesses and lead to improvements in Public Health.
Thesaurus Terms: Accelerated Interstitial Pneumonitis;Acute Interstitial Pneumonitis;Amyloid;Amyloid Substance;Animal Model;Animal Models And Related Studies;Assay;Bioassay;Biologic Assays;Biological;Biological Assay;Biological Function;Biological Process;Blood Cells;Blood Serum;Bone Marrow;Cell Count;Cell Number;Cells;Clinical;Common Rat Strains;Desquamative Interstitial Pneumonitis;Development;Disease;Disorder;Drug Delivery;Drug Delivery Systems;Drug Evaluation, Preclinical;Drug Screening;Drug Targeting;Drug Targetings;Drugs;Evaluation Studies, Drug, Pre-Clinical;Evaluation Studies, Drug, Preclinical;Fda Approved;Fibroblasts;Fibrosing Alveolitis;Fibrosis;Goals;Hamman-Rich Syndrome;Healing Abnormal;Healing Delayed;High Throughput Assay;Idiopathic Ards;Idiopathic Interstitial Pneumonia;Impaired Healing;Impaired Tissue Repair;Impaired Wound Healing;In Vitro;Injection Of Therapeutic Agent;Injections;Investigators;Lead;Libraries;Lung Diseases;Mammals, Mice;Mammals, Rats;Mediator;Mediator Of Activation;Mediator Of Activation Protein;Medication;Methods;Methods And Techniques;Methods, Other;Mice;Modeling;Morbidity;Morbidity - Disease Rate;Mortality;Mortality Vital Statistics;Murine;Mus;Non-Specific Interstitial Neumonia/Fibrosis;Pbmc;Pathway Interactions;Pb Element;Peripheral Blood Cell;Peripheral Blood Mononuclear Cell;Pharmaceutic Preparations;Pharmaceutical Preparations;Phase;Population;Preclinical Drug Evaluation;Proteins;Public Health;Pulmonary Diseases;Pulmonary Disorder;Pulmonary Fibrosis;Rat;Rattus;Research Personnel;Researchers;Respiratory Disease;Respiratory Disorder;Respiratory System Disease;Respiratory System Disorder;Reticuloendothelial System, Bone Marrow;Sbir;Sbirs (R43/44);Serum;Small Business Innovation Research;Small Business Innovation Research Grant;Techniques;Usual Interstitial Pneumonia;Usual Interstitial Pneumonitis;Variant;Variation;Abnormal Tissue Repair;Base;Cell Type;Delayed Wound Healing;Diffuse Interstitial Pulmonary Fibrosis;Disease /Disorder;Disease/Disorder;Drug /Agent;Drug Discovery;Drug/Agent;Effective Therapy;Gene Product;Heavy Metal Pb;Heavy Metal Lead;High Throughput Screening;Idiopathic Pulmonary Fibrosis;In Vivo;Inhibitor;Inhibitor /Antagonist;Inhibitor/Antagonist;Innovate;Innovation;Innovative;Library;Lung Disorder;Model;Model Organism;Pathway;Public Health Medicine (Field);Small Molecule
