Overproduction of Sirt6 Protein Protects Against Pulmonary Fibrosis Lung Damage, Study Reports
Overproduction of a protein called Sirtuin 6 (Sirt6) inhibits a cell process essential to the lung scarring seen in pulmonary fibrosis, according to a study.
The finding suggests that scientists could use Sirt6 to develop therapies that prevent the disease. Scientists call the process that the finding applies to the epithelial to mesenchymal transition (EMT) cell process.
Expression is the process by which a gene creates a functional product such as a protein. Overexpression means it is producing too many copies of the protein. The study centers on overexpression of Sirt6.
A hallmark of lung fibrosis is an accumulation of fibroblasts, or connective-tissue cells. The accumulation leads to the production of excessive amounts of proteins such as collagen, making lung tissue less flexible and reducing lungs’ respiratory capacity.
At that same time that fibroblasts are producing excessive amounts of protein, the EMT process is occurring. This is the transformation of epithelial cells, which line hollow organs and glands, into mesenchymal or fibroblast-like connective-tissue cells.
Together, these mechanisms lead to gradual deterioration of lung tissue and impairment of respiratory capacity. Scientists have yet to understand what triggers or regulates the processes.
Researchers wanted to learn how Sirt6 is involved in lung fibrosis. Their study, “Sirtuin 6 inhibits epithelial to mesenchymal transition during idiopathic pulmonary fibrosis via inactivating TGF-β1/Smad3 signaling,” was published in Oncotarget.
Sirt6 has been associated with aging and cancer, but scientists believe it helps prevent cardiac and liver fibrosis.
When the researchers forced the overexpression of Sirt6 in human lung cells in a lab, they discovered that the excessive protein production inhibited the EMT process that often occurs in idiopathic pulmonary fibrosis.
In addition, they found that overexpression of the protein inhibited a cascade of cell signals that trigger EMT and regulate the expression of several genes associated with it.
To confirm Sirt6’s role in underlying mechanisms of pulmonary fibrosis, the team forced the expression of the protein in the lungs of mice as well. The result was less EMT transformation in the animals’ lung cells, which prevented them from developing as much fibrosis.
Although the researchers were unable to stop the fibrotic process completely, their findings added new pieces to the complex puzzle involved in the development of pulmonary fibrosis.
“In summary, we identified that Sirt6 suppressed EMT phenotype in vivo [in animals] and in vitro [in a lab],” the researchers wrote. This suggested that “Sirt6 may be an attractive potential therapeutic target for idiopathic pulmonary fibrosis,” they noted.
The team now plans studies that target Sirt6 as a way to develop pulmonary fibrosis treatments.