FOXF1 Inhibits Idiopathic Pulmonary Fibrosis, May Serve as Target for New Treatments
Published April 10, 2018 | Cell Reports
Scientists searching for a therapy to stop deadly, hard-to-treat idiopathic pulmonary fibrosis (IPF) have identified a new molecular target that slows or stops the illness in preclinical laboratory tests.
IPF primarily affects people between ages 50 and 70, but it can strike younger adults and children. About 100,000 people are affected in the United States, with up to 40,000 new cases diagnosed a year.
The disease includes extensive scarring in lung connective tissues, hyperproduction of harmful myofibroblasts, and excessive lung inflammation.
The precise causes of IPF remain unknown, but genetic predisposition, smoking and other potential environmental factors are suspected.
A research team led by first author Markaisa Black, PhD, and senior author Tanya Kalin, MD, PhD, reports that the gene FOXF1 inhibits the IPF disease process. FOXF1 is a transcription factor that acts as a molecular switch for two other genes, CDH2 and CDH11.
When triggered, the gene induces CDH2, but inhibits CDH11 to shut down IPF—a pathway that fails to activate when FOXF1 is missing.
The team learned that human lungs from IPF patients and mouse models of IPF both lack FOXF1 in myofibroblasts. Those cells also overexpress the gene FOXM1, which drives lung scarring and inflammation.
“We are developing different therapeutic approaches and conducting preclinical tests to increase FOXF1 expression in the cells of lung connective tissues,” Kalin says.
This work includes testing a novel small-molecule compound that stabilizes FOXF1 and inhibits myofibroblasts in IPF. Researchers also are testing a nanoparticle-based gene delivery method.
