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. 4 July 2018
The researchers succeeded for the first time in reversing idiopathic pulmonary fibrosis. Although rare, this form of pulmonary fibrosis is particularly aggressive. It was a well tried drug, which affects the metabolism in the cells.
Up to now, there is no way to effectively treat pulmonary fibrosis. Researchers at the University of Alabama at Birmingham are now introducing a new approach in a study. In their experiments, they examined the lung tissue of patients with idiopathic pulmonary fibrosis (IPF), a special form that is aggressive and poorly cultured.
The research team relied on a long-approved drug: for the treatment of diabetes. Using metformin, the team was able to eliminate the IPF
Resistant Cells
The objective of the research was AMP kinase-dependent (AMPK). It is an enzyme that recognizes the energy status of cells and regulates metabolism. Zmijewski, Thannickal and their colleagues noted that in IPF patients, the activity of AMPK in myofibroblasts of lung tissue was clearly low. During the fibrosis process, myofibroblasts deposit extracellular collagen fibers. These low AMPK activity myofibroblasts were metabolically more active and resistant to apoptosis.
The activation of AMPK in myofibroblasts in the lungs of IPF patients through the use of metformin resulted in lower fibrotic activity. The same effect was observed when using the activator of AMPK AICAR ( 5-aminoimidazole-4-carboxamide ribonucleotide ).
This activation also promotes the production of new mitochondria in myofibroblasts, responsible for the generation of new energy are responsible. Cells also responded again to apoptotic signals
What role does metformin play?
In addition to human tissue, scientists also badyzed mouse fibroblasts. The research team also used a mouse model of pulmonary fibrosis triggered by the use of bleomycin. This medicine is used to treat testicular tumors. Known side effects of bleomycin include pulmonary fibrosis. On the model of the mouse, they wanted to know how a drug works with metformin.
Scientists began treatment three weeks after lung injury. Five weeks after the start of treatment, the team observed that metformin accelerates the resolution of fixed fibrosis. In mice whose AMPK was suppressed, this effect did not occur. From there, the experts concluded that the effect of metformin should be dependent on the AMPK
Confident Study Authors
"Our studies support the concept that AMPK could act as a switch Metabolic key to help resolution of existing fibrosis.The balance between anabolic and catabolic metabolism is offbeat, "explain the study authors.The use of metformin may be a useful therapeutic strategy for progressive fibrotic disorders
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