Idiopathic pulmonary fibrosis (IPF) is an aging-associated disease caused by\u00a0progressive\u00a0scarring of the lungs, leading to respiratory failure and death. Therapies to treat IPF are limited, making studies on the mechanisms responsible for this crippling disease a priority. Now for the first time, researchers at the Arthritis and Autoimmune Diseases Center (AADC) at Boston University School of Medicine (BUSM) in collaboration with those at Mayo Clinic, Rochester, Minn., have discovered a new mechanism linking the aging of blood vessels to the development of pulmonary fibrosis.<\/p>\n
More specifically, they found that ERG, a protein that normally controls the regenerative properties of endothelial cells (the inner lining of blood vessels), is implicated in the progression of IPF, an aging-associated disease that causes progressive\u00a0scarring of the lungs, respiratory failure and death.<\/p>\n
\u201cAlthough the lungs of IPF patients manifest multiple vascular abnormalities, the contribution of these alterations to the progression of IPF has remained largely unexplored. \u201cOur findings demonstrated the impact of the aged lung vasculature on the pathogenesis of IPF,\u201d said corresponding author Giovanni Ligresti, PhD, associate professor of medicine at BUSM. \u201cThis work is also relevant to other fibrotic disorders, including lung fibrosis associated with scleroderma,\u201d said BUSM professor of medicine Maria Trojanowska, PhD, director of the AADC and collaborator of this study.<\/p>\n
The researchers used experimental models of pulmonary fibrosis, human lung cells and lung tissues from human patients with IPF to investigate how aging-associated dysfunction of the pulmonary vasculature contributes to the progression of IPF.<\/p>\n
In addition, they created a new experimental model in which the gene ERG was depleted from blood vessels. \u201cUpon lung injury, models with deleted ERG were no longer able to properly repair from the injury resulting in progressive lung scarring as observed in aged mice, as well as in patients with IPF. Furthermore, even in absence of injury, models without ERG exhibited features of advanced aging, including increased inflammation and an enhanced predisposition to develop chronic conditions, which are typically observed in elderly,\u201d explained Ligresti.<\/p>\n
According to the researchers, given that many chronic diseases in elderly are characterized by dysfunctional blood vessels, targeting molecular mechanisms that can promote blood vessel regeneration, such as ERG, will be beneficial in multiple organs besides lungs. \u201cThese findings may also have important implications in elderly patients with COVID-19, in which vascular abnormalities and elevated vascular inflammation are\u00a0often responsible for disease exacerbation and death,\u201d adds Ligresti.<\/p>\n