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Lung Fibrosis can be Reduced by Restoring Lipid Synthesis in the Lungs

by Rishika Gupta on March 6, 2018 at 10:37 AM
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 Lung Fibrosis can be Reduced by Restoring Lipid Synthesis in the Lungs

Body's ability to produce lipids in the lungs could be enhanced to prevent the progression of pulmonary fibrosis, finds a new study. The findings of this study are published in the American Journal of Respiratory Cell and Molecular Biology.

Pulmonary fibrosis is an ongoing process of scarring that can leave patients most affected chronically short of breath. It can also progress further in severity until the only course of treatment is lung transplant.


"This is the first paper to show that rather than being a 'second hit' to help initiate the disease, blocking lipid synthesis alone -- with no other insult to the lungs -- can instigate fibrotic scaring," said Ross Summer Professor of Medicine at Thomas Jefferson University and physician-researcher in the Jane and Leonard Korman Respiratory Institute.

"This suggests that failure to produce lipids, perhaps because of injury or age-related metabolic changes in lung cells, may be an underappreciated process in development of lung fibrosis, one that may also offer a new and potentially easier path to new treatment of this disease," said Dr. Romero lead author and NIH-funded investigator on the study published Feb 21st in the American Journal of Respiratory Cell and Molecular Biology.

Surfactants, or lipids produced inside the lung tissue, allow airways to inflate and deflate with ease. In fact, surfactants are often one of the first treatments given to a premature infant to help ensure the lungs inflate and develop properly.

In addition, all cells within the lung need lipids as signaling molecules and to build their internal and external membranes. But in earlier work, Dr. Summer and Romero have shown that when lung tissue is injured -- by things like viral infection, particulate inhalation, or other insults -- lung cells eventually stop producing lipids in order to conserve energy for other cellular repairs.

In this study, the teams of Drs. Summer and Romero used a drug that inhibited lipid production in the lung and showed that this drug alone was capable of instigating lung fibrosis. In the converse experiment, the group showed that when increasing lipid production in lungs of animals already injured and developing pulmonary fibrosis, lung scarring could be reduced by 70-80 percent.

Lung fibrosis is thought to also come about when the endoplasmic reticulum (ER) in the cells of the lung becomes stressed and can no longer properly fold and unfold proteins. "We think that the chronic ER stress might ensue because of the inability of cells to produce sufficient lipids to supply their vast amount of ER membranes. Without appropriate lipid stores, the ER cannot properly manufacture or remove damaged proteins out of the cell into lysosomes; as a result, damage accumulates in these lung cells leading to irreversible fibrosis."

Dr. Summer and colleagues are currently working to develop a therapy that could restore lipid production in the lungs of pulmonary fibrosis patients and slow the fibrotic process. As a physician who treats patients with pulmonary fibrosis in a multidisciplinary clinic at Jefferson, the research has a sense of urgency. "I'd like to be able to offer my patients better options for this disease," he said.

Source: Eurekalert

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