Aspirin shows benefits in cell, mouse models of pulmonary fibrosis

Over-the-counter medicine found to ease scarring in new study

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The use of aspirin, a common over-the-counter medicine, showed benefits in mouse and cell models of pulmonary fibrosis (PF) in a recent study, reducing evidence of scarring.

The medication seemed to exert its beneficial effects by promoting a cellular maintenance process called autophagy, during which cells break down and recycle old or damaged molecules.

“Aspirin may be beneficial in the protection of pulmonary fibrosis,” the researchers wrote, noting that future studies should further investigate the medicine’s therapeutic potential in the chronic lung disease.

The study, “Aspirin alleviates pulmonary fibrosis through PI3K/AKT/mTOR-mediated autophagy pathway,” was published in the journal Experimental Gerontology.

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Investigating the benefits of aspirin use in PF

PF is marked by progressive scar tissue buildup — fibrosis — and inflammation in the lungs. The disease, for which there is no cure, still has limited treatment options.

Aspirin is a medication that can be purchased without a prescription and is commonly used to alleviate pain, fever, and inflammation. It’s also used preventively in people at risk of developing cardiovascular disease.

Recent research indicates that aspirin also has anti-fibrotic effects in the liver, heart, and uterine lining. This may be due to its ability to inhibit the P13K/AKT/mTOR signaling pathway that regulates autophagy.

It has been suggested that autophagy has anti-fibrotic effects — with autophagy impairments linked to accelerated lung fibrosis. Tissues from patients with idiopathic pulmonary fibrosis (IPF), in which the underlying cause of the disease is unknown, also have been reported to show signs of insufficient autophagy.

Altogether, this suggests that aspirin could have benefits for people with PF. However, its potential role in the disease hasn’t been investigated. Thus, a team of researchers in the U.S. and China explored this possibility in a joint study.

First, they turned to a cell culture model of fibrosis using cells called fibroblasts. The activation of these cells and their differentiation into myofibroblasts is thought to be a key process driving fibrosis in PF.

Aspirin treatment was able to significantly reduce the activity of fibrosis-related genes and slow cell migration in the PF model, suggesting that treatment had anti-fibrotic effects.

Autophagy seemed to be enhanced with aspirin treatment, as reflected by an increase in the levels of a protein called LC3B, and a decrease in those of another protein known as SQSTM1. Similar findings were observed in lung cells taken from IPF patients.

The anti-fibrotic effects of aspirin were reversed when cells were treated with autophagy inhibitors, suggesting that the treatment’s beneficial effects were indeed mediated by that process.

Moreover, researchers found that aspirin worked to enhance autophagy by inhibiting the P13K/AKT/mTOR signaling pathway. The levels of these proteins were diminished in aspirin-treated cells, as were some of their downstream signaling molecules.

Treatment with an AKT activator was able to overcome this suppression and prevent aspirin’s anti-fibrotic effects. Activation of the P13K/AKT/mTOR signaling pathway has been previously implicated in PF.

Further studies are needed to confirm that aspirin might serve as a potential therapeutic drug for the treatment of pulmonary fibrosis.

The findings overall were similar in a mouse model of induced PF. Animals given aspirin every day for about a month had less tissue injury and inflammation than untreated mice, as well as significant reductions in lung fibrosis.

Consistent with cell culture findings, aspirin-treated mice had increased levels of LC3B and reduced SQSTM1, reflecting an enhancement in autophagy. Autophagosomes, the structures that form to mediate autophagy, also were increased with aspirin treatment.

In general, these findings support the potential protective effects of aspirin for PF via its effects on autophagy, according to researchers.

“Further studies are needed to confirm that aspirin might serve as a potential therapeutic drug for the treatment of pulmonary fibrosis,” the team wrote.