A small RNA molecule, called microRNA 101, prevents the proliferation and activation of fibroblasts, thereby eliminating pulmonary fibrosis (PF) in mice, researchers at Oklahoma State University (OSU) have found.
Their study, “MicroRNA-101 attenuates pulmonary fibrosis by inhibiting fibroblast proliferation and activation,” appeared in the Journal of Biological Chemistry.
Abnormal activity and proliferation of fibroblasts leads to increased production of collagen, contributing to fibrosis. Yet the mechanisms underlying proliferation and activation of lung fibroblasts remain unclear.
Several small RNA molecules, called microRNAs, have been implicated in lung diseases including idiopathic lung fibrosis (IPF). They regulate gene and protein expression, and therefore greatly affect how cells behave.
Previous studies showed that microRNAs are tightly regulated in PF, suggesting their essential role in causing this disease. Based on this hypothesis, investigational therapies targeting specific microRNAs are now being developed to help patients with lung fibrosis.
“Emerging evidence suggests that suppressing up-regulated [increased] miRNAs or restoring the activities of the down-regulated [decreased] miRNAs associated with disease could become a novel therapeutic strategy,” researchers wrote.
OSU researchers and their colleagues analyzed levels of several microRNAs in 28 lung tissue samples of IPF patients that were available through the Lung Tissue Research Consortium.
They found that levels of one microRNA molecule — microRNA 101 — were particularly low in patients with severe IPF compared to those with more normal lung function. In addidtion, microRNA101 levels were also downregulated in lung tissue collected from mice with bleomycin-induced PF, a well0established model of the disease.
Other experiments showed that fibroblast behavior changed according to levels of expression of microRNA 101. Indeed, by increasing expression of microRNA 101 in fibroblasts, researchers could prevent their proliferation and activation. One of the targets of microRNA 101, researchers found, was a receptor for the transforming growth factor (TGF)-beta, the primary factor driving fibrosis.
Next the researchers manipulated mice to force the expression of microRNA 101 in their lungs. Mice treated with microRNA 101, they found, had less fibrosis and less collagen deposition compared to control animals. Importantly, higher levels of microRNA 101 also improved the animals’ lung function.
Overall, the study concluded, “microRNA-101 is an anti-fibrotic microRNA and a potential therapeutic target for pulmonary fibrosis.”