GDF-15 May be Marker of Poor IPF Prognosis

The protein GDF-15 is expressed in low concentrations in most organs and is upregulated with injury. GDF-15 is thought to have role in regulating inflammatory pathways and was previously shown to be a strong prognostic protein in patients with different diseases such as heart diseases and cancer.

The study “GDF15 is an epithelial-derived biomarker of idiopathic pulmonary fibrosis,” published in the American Journal of Physiology, examined  GDF-15 in the context of idiopathic pulmonary fibrosis (IPF).

IPF is the most common type of interstitial lung disease, which is characterized by scarring (fibrosis) of the lung tissue.

A team led by University of Pittsburgh researchers developed an experimental animal model in which type II alveolar epithelial cells, or AEC2s, were modified to undergo DNA instability and to stop growing. These mice developed pulmonary inflammation 14 to 21 days after epithelial deregulation was induced.

Using this animal model, researchers sought to characterize the signals that were changed by the dysfunctional epithelium as a means to identify potential biomarkers indicative of IPF.

By looking at gene production signatures, the team found that the protein GDF-15 was the most significantly upregulated upon an AEC2s imbalance.

Next, they confirmed that GDF-15 levels also were higher in mice that had been exposed to bleomycin, a pulmonary toxin widely used to induce experimental IPF symptoms. This suggests that GDF-15 upregulation is associated with the pro-inflammatory signals involved in IPF, rather than just being an artifact of the experimental procedures used.

To examine the relevance of GDF-15 in human IPF, the researchers evaluated clinical samples collected from 134 IPF patients and 108 age-matched controls, stored by the Lung Genomics Research Consortium.

The data showed that GDF-15 protein levels were increased in both blood and lung tissue from people with IPF compared with controls — and that it correlated with patients’ pulmonary function. The highest GDF-15 levels were found in people who had more severe disease and poorer outcomes. GDF-15 also was found to be highly present in lung areas that were more damaged, or that showed increased signs of fibrosis.

These results identify GDF-15 as a new cell-specific marker of epithelial injury, as well as a new biomarker of IPF severity.

“Our data suggest that GDF-15 is a novel epithelial ‘stress signal’ and biomarker of IPF that identifies patients with severe, progressing disease,” the researchers said.

Adapted from pulmonaryfibrosisnews.com