Inhibiting Inflammation-promoting Enzyme Slows Lung Tissue Scarring, Mouse Study Shows


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Inhibiting enzyme

Inhibiting an inflammation-promoting enzyme known as sialidase slowed lung tissue scarring in mice with pulmonary fibrosis, a study shows.

The research indicated that sialidase inhibitors, such as Tamiflu, could be used to treat idiopathic pulmonary fibrosis, or IPF.

The underlying causes of fibrosis in diseases such as IPF and asthma are still unclear. Several studies have suggested that a type of protein known as a glycoprotein, which contains sialic acid, can suppress the inflammation associated with lung tissue scarring, or fibrosis. Sialic acids are sugar molecules that help regulate a variety of the body’s functions.

Sialidases counter sialic acids. By remove the acids from glycoproteins, sialidases promote inflammation.

A previous study showed that sialidases are more active in IPF patients than in healthy controls and that there is a correlation between sialidases activity and the progression of the disease.

This prompted researchers to decide to see whether inhibiting sialidases would slow lung scarring.

The study, “Sialidase inhibitors attenuate pulmonary fibrosis in a mouse model,” was published in the journal Scientific Reports.

Researchers first examined the levels of four sialidases — NEU1, NEU2, NEU3 and NEU4 — in tissue from humans with IPF and in a mouse model of lung fibrosis. As a control, the team compared scarring in human IPF tissue with scarring in the tissue of COPD patients.

IPF patients had higher levels of NEU2, NEU3 and NEU4 in their lungs than COPD patients, researchers found. Similarly, NEU1, NEU2 and NEU3 levels were higher in fibrotic mice than in healthy mice.

Researchers also experimented with human IPF cells grown in a lab. A key finding was that TGF-β1, a protein associated with tissue scarring, promoted sialidases activity in the cells.

In fact, the researchers discovered a feedback loop between TGF-β1 and sialidases. The key finding there was that high levels of sialidase increased levels of TGF-β1.

When the team treated the fibrosis mice with a sialidase inhibitor — either DANA or Tamiflu — scarring slowed. In addition, the inhibitors reduced levels of TGF-β1 and sialidase.

The fact that the TGF-β1-sialidases feedback loop promotes scarring suggests that “sialidase inhibitors could be useful for the treatment of fibrosis,” the team concluded.