Diseased lung, conceptual illustration to illustrate pulmonary fibrosis
Credit: SEBASTIAN KAULITZKI/SCIENCE PHOTO LIBRARY/Getty Images

Researchers at the Boston University School of Medicine (BUSM) in collaboration with the Mayo Clinic have identified a protein linking the aging of blood vessels to the development of pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an aging-associated disease caused by the progressive inflammation and scarring of lung tissue, eventually leading to respiratory failure and death. Despite thousands of people in the U.S. suffering from the illness, with nearly 45% of COVID survivors developing the disease, therapies to treat IPF are limited making further research on its underlying mechanisms a priority.

A new study published in Nature Communications has now identified a protein known as ERG that is normally involved in the regeneration of endothelial cells to be dysregulated in patients with IPF leading to permanent scarring of lung tissue due to abnormal cytoskeletal processes.

“Our findings demonstrated the impact of the aged lung vasculature on the pathogenesis of IPF,” said professor of medicine at BUSM and co-author of the study Giovanni Ligresti in a press statement.

By creating an experimental model in which the ERG protein was removed from blood vessels in lungs, the researchers were able to demonstrate that upon injury the models were no longer able to repair lung tissue, making ERG a possible marker for the disease. Even in absence of injury, models without ERG exhibited features of advanced aging, including increased inflammation and an enhanced predisposition to develop chronic conditions.

“These findings may… have important implications in elderly patients with COVID-19, in which vascular abnormalities and elevated vascular inflammation are often responsible for disease exacerbation and death,” Ligresti added.

Previous attempts at IPF treatments have included the use of nanoparticles targeting innate immune cells in a bid to stop the acute inflammatory response leading to tissue scarring with promising results.

“The ideal treatment would be an epigenetic intervention, by using a drug that would allow ERG to work better in the elderly, possibly by unmasking the DNA sites that are otherwise unavailable to ERG with aging,” Nunzia Caporarello, assistant professor at the Mayo Clinic and co-author of the study told Inside Precision Medicine.

The results of the study add to previous research, published in JCI Insight, where another protein known as SREBP2 was shown to be overexpressed in epithelial cells, causing increased scarring of lung tissue by remodeling the cytoskeleton and also posing as a potential marker for IPF.

According to the researchers at BUSM targeting ERG in epithelial cells could also improve a variety of other health conditions in elderly people caused by degenerating blood vessels. “This work is also relevant to other fibrotic disorders, including lung fibrosis associated with scleroderma,” said Maria Trojanowska, BUSM professor of medicine and co-author of the study, in a press statement.

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