Thyroid hormone, a potential therapy for lung fibrosis
Pulmonary fibrosis is a life-threatening disease that usually affects old people, particularly those with a history of smoking. In pulmonary fibrosis, scars are formed in the lung, impairing lung function. People with pulmonary fibrosis often experience tiredness, coughing, shortness of breath, diminished exercise tolerance, and other symptoms. To date, there are no effective treatments to cure lung damage in pulmonary fibrosis.
Most cases of pulmonary fibrosis have no known cause, and these cases are collectively known as idiopathic pulmonary fibrosis (IPF). The progression of IPF is generally irreversible and unpredictable. The amount of lung scarring usually increases over time and the damage to the lungs is permanent. The mortality of IPF is even higher than many types of cancer, including colon and bladder cancer. More than half of patients with IPF die within 5 years after diagnosis.
According to a new study by Yale School of Medicine researchers, thyroid hormone could inhibit lung fibrosis in mouse models of IPF by improving mitochondrial function. The discovery would lead to new therapies for the fatal disease IPF in humans. In addition to Yale researchers, researchers from Rush University Medical Center, the Salk Institute for Biological Studies, and Oregon Health and Science University also participated in the study. The paper, titled "Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function," appeared online in Nature Medicine on 4 December 2017.
Analyzing gene expression profiles in the lungs, the researchers found that patients with IPF had higher levels of DIO2 expression in their lungs compared to controls and that DIO2 expression was associated with disease severity. The protein encoded by the DIO2 gene is an enzyme known to activate thyroid hormone. Thyroid hormone plays an important role in the regulation of cellular homeostasis.
Further, the researchers discovered that mice lacking DIO2 showed increased bleomycin-induced lung fibrosis. When the researchers tested thyroid hormone and its mimetic in different mouse models of pulmonary fibrosis, they found that treatment with thyroid hormone or its mimetic was able to alleviate lung fibrosis in the mice and improve the animals' survival, suggesting that thyroid hormone has antifibrotic properties. Further experiments revealed that thyroid hormone helped restore the function of mitochondria in alveolar epithelial cells.
There is evidence that epithelial cell mitochondrial dysfunction is implicated in pulmonary fibrosis. Combining this information with the findings, the researchers speculated that the antifibrotic properties of thyroid hormone may be due to its protective effects on mitochondrial function. Thyroid hormone holds promise in treating pulmonary fibrosis in humans. But more research is needed to assess its safety and effectiveness.
According to Naftali Kaminski, who is one of the researchers participating in the study and who is a professor of medicine at Yale School of Medicine, how thyroid hormone is delivered is important. When delivered systemically, thyroid hormone may trigger hyperthyroidism. When delivered by aerosol, thyroid hormone may reduce fibrosis without triggering hyperthyroidism.
Professor Kaminski is committed to studying the basic mechanisms and improving the management of chronic lung diseases, such as IPF, severe asthma and sarcoidosis. To achieve this goal, he uses various genomic methods.
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