A transcription factor called ERG could be controlling the homeostasis and repair of capillary blood vessels in the lungs, according to a new study published in Nature Communications.

The study also found that the function of ERG is dysregulated in aging and that this leads to reduced chromatin accessibility and impairs transcriptional responses to injury. In the absence of ERG in endothelial cells, fibroblasts are activated impairing the resolution of lung fibrosis.

Together, these findings demonstrate that the remodeling of lung endothelial chromatin deteriorates with age and that this leads to abnormal transcription, vascular repair, and persistent fibrosis after injury. They can, therefore, help explain how endothelial aging can be linked to idiopathic pulmonary fibrosis (IPF) and are critical for the development of new strategies to slow the progression of the disease.


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“Our findings demonstrated the impact of the aged lung vasculature on the pathogenesis of IPF,” said Giovanni Ligresti, PhD, from the Department of Medicine at Boston University School of Medicine in Massachusetts.

The team used a mouse model of IPF as well as human lung cells, and lung tissue from patients with IPF to investigate the effect of aging on the pulmonary vasculature and how this may contribute to the progression of IPF. They showed that the lungs of mice deficient in ERG display transcriptional and fibrogenic abnormalities that are similar to those associated with aging and human lung fibrosis including a lower number of general capillary endothelial cells.

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“Our results shed light on the role of pulmonary [endothelial cells] in the progression of lung fibrosis, shifting their role from passive bystander to an active driver of fibrosis,” the researchers concluded.

IPF is a progressive disease of unknown etiology associated with aging. There are currently no effective treatments for the disease so it is paramount to better understand the mechanisms underlying its development and progression to be able to develop better and more effective treatments.

Reference

Caporarello N, Lee J, Pham TX, et al. Dysfunctional ERG signaling drives pulmonary vascular aging and persistent fibrosis. Nat Commun. 2022;13(1):4170. doi:10.1038/s41467-022-31890-4