Lung Fibrosis Development in Mice Controlled by MicroRNA, Study Shows

Researchers at the Chinese Nanjing University School of Medicine in China discovered yet another microRNA that contributes to the development of lung fibrosis. MicroRNA are small molecules known to control gene activity.

The study, “MiR-338* suppresses fibrotic pathogenesis in pulmonary fibrosis through targeting LPA1,” published in the American Journal of Translational Research, also revealed that boosting the production of this factor ensured a milder lung fibrosis development in mice, which suggests that the microRNA may be a good target for future treatment.

MicroRNA molecules are factors that in recent years have attracted plenty of attention in different research fields. Because they act by controlling whether genes are switched on or off, they are involved in numerous disease processes. Researchers believe that microRNAs can be controlled to harness diseases such as lung fibrosis.

Earlier research found that the microRNA called miR-338* was linked to lung fibrosis in rats. In this study, Nanjing scientists first looked at the levels of the microRNA in human cells grown in the lab. They noted that if cells were exposed to the pro-fibrotic factor TGF-beta, miR-338* levels dropped.

The team then triggered lung fibrosis development in mice by exposing them to bleomycin and then observed again that the microRNA levels were lower in mice with lung fibrosis compared to normal mice.

To test whether it was possible to reverse this development, the team first increased the production of miR-338* in normal human airway cells that had turned fibrotic after exposure to TGF-beta. Using powerful microscopy, researchers tracked changes in the cells’ appearance. Normal cells exposed to TGF-beta began to look more like the fibrosis-promoting fibroblast cell type, but when levels of the microRNA went up the cells regained their normal appearance.

Researchers also identified a gene controlled by miR-338* and found that high levels of the microRNA switched off the activity of the LPA1 gene. They also confirmed that the activity of this gene was sufficient to change the appearance of the cells.

The same thing was observed in mice with lung fibrosis. After 14 days researchers boosted the production of miR-338* in the animals and observed how lung fibrosis became milder. Again, the effects were dependent on the LPA1 gene.

As previously reported by Pulmonary Fibrosis News, the company miRagen Therapeutics is developing an antifibrotic treatment targeting another microRNA molecule. The drug candidate is in Phase 1 clinical trials.