Researchers at the University of Alabama at Birmingham have shown — for the first time — that established lung fibrosis can be reversed using a drug treatment that targets cell metabolism.
This novel finding, reported in the journal Nature Medicine, is important because, despite significant advances to reveal the pathological mechanisms of persistent fibrosis, effective treatment interventions are lacking.
Pulmonary fibrosis can develop after lung injuries like infections, radiation or chemotherapy, or it can have an unknown cause, as in idiopathic pulmonary fibrosis, or IPF. IPF is a progressive, and ultimately fatal, lung disorder that strikes more than 150,000 patients a year in the United States and more than 5 million worldwide.
In experiments using lung tissues from patients with IPF, mouselung fibroblasts and a murine model of lung fibrosis, a team led by Jaroslaw Zmijewski, Ph.D., and Victor Thannickal, M.D., showed the reversal of lung fibrosis and the underlying cellular mechanisms affected by the drug treatment.
Zmijewski and Thannickal are, respectively, associate professor and professor in the UAB Department of Medicine. Zmijewski serves as research director for the Translational Program in ARDS. Thannickal holds the Ben Vaughan Branscomb Chair of Medicine in Respiratory Disease and is director of the UAB Division of Pulmonary, Allergy and Critical Care Medicine.
|Activation of AMPK in myofibroblasts from lungs of humans with IPF, using the drug metformin or another activator called AICAR, led to lower fibrotic activity. AMPK activation also enhanced the production of new mitochondria, the organelles in cells that produce energy, in the myofibroblasts, and it normalized the cells’ sensitivity to apoptosis.|
Interestingly, the drug that accelerated the resolution of lung fibrosis is metformin, which is a safe and widely used agent for non-insulin-dependent diabetes.
The research focused on AMP-activated protein kinase (AMPK), an enzyme that senses energy state in the cell and regulates metabolism. Zmijewski, Thannickal and colleagues found that AMPK activity was lower in myofibroblast cells within fibrotic regions of human lung tissue from IPF patients. Myofibroblasts deposit extracellular collagen fiber as part of the fibrosis process. These myofibroblasts were metabolically active and were resistant to the programmed cell death called apoptosis, a natural process that removes more than 50 billion damaged or aged cells in adults each day.
Activation of AMPK in myofibroblasts from lungs of humans with IPF, using the drug metformin or another activator called AICAR, led to lower fibrotic activity. AMPK activation also enhanced the production of new mitochondria, the organelles in cells that produce energy, in the myofibroblasts, and it normalized the cells’ sensitivity to apoptosis.
Using a mouse model for lung fibrosis elicited by the anti-cancer drug bleomycin, the research team found metformin treatment, starting three weeks after lung injury and continuing for five weeks, accelerated the resolution of well-established fibrosis. Such resolution was not apparent in AMPK-knockout mice, showing that the effect of metformin was AMPK-dependent.
“Together, our studies support the concept that AMPK may function as a critical metabolic switch in promoting resolution of established fibrosis by shifting the balance from anabolic to catabolic metabolism,” the researchers wrote. “Additionally, we provide proof-of-concept that activation of AMPK by metformin or other pharmacologic agents that activate these pro-resolution pathways may be a useful therapeutic strategy for progressive fibrotic disorders.”
Anabolic metabolism builds up molecules in the cell from smaller units, while catabolic metabolism tears larger molecules into smaller pieces.
Learn more: Metformin reverses established lung fibrosis
The Latest on: Pulmonary fibrosis
via Google News
The Latest on: Pulmonary fibrosis
- Chemist Richard Van Duyne Dieson August 16, 2019 at 11:51 am
Richard Van Duyne, a chemist at Northwestern University and a pioneer in the development of techniques in analytical chemistry, died late last month (July 28) from pulmonary fibrosis. He was 73. Van ...
- Pulmonary Fibrosis Market by Company Profile, Product Specifications, Capacity, Production Value and Forecast 2025on August 16, 2019 at 8:09 am
Pulmonary fibrosis is a condition identified by the scarring or damage of lung tissues, making breathing difficult in patients suffering from the condition. There are various causes that may lead to ...
- Respiratory Monitoring Market To Experience Significant Growth During The Forecast Period 2016-2022on August 16, 2019 at 3:13 am
Some of the chronic respiratory diseases are acute respiratory distress syndrome, asthma, chronic obstructive pulmonary disease, cystic fibrosis, pulmonary fibrosis, pneumonia, respiratory failure, ...
- EmphyCorp Inc. FDA Submission for Rx New Non-Steroidal Nasal Spray for Pulmonary Fibrosis w/ No Known Side Effectson August 15, 2019 at 7:08 am
FLEMINGTON, N.J., Aug. 15, 2019 /PRNewswire/ -- EmphyCorp Inc. www.EmphyCorp.com, a Private Corporation, is proud to announce the completion of a clinical trial to define medical endpoints as ...
- Making a 'Working Diagnosis' of Idiopathic Pulmonary Fibrosison August 15, 2019 at 6:25 am
Classification of interstitial lung disease (ILD) is challenging.  The most common and best studied ILD is idiopathic pulmonary fibrosis (IPF). Still, it makes up only one third of all ILD cases, ...
- aTyr Pharma, Inc. (LIFE) CEO Sanjay Shukla on Q2 2019 Results - Earnings Call Transcripton August 14, 2019 at 5:37 pm
We are focused on all forms of ILDs with the exception of idiopathic pulmonary fibrosis, or IPF, which is the least inflammatory ILD. Inflammatory ILDs represent a unique area of opportunity where ...
- Idiopathic Pulmonary Fibrosis Treatment Market is Worth US$ 4.2 Bn By 2026on August 14, 2019 at 4:38 am
Aug 14, 2019 (Global QYResearch via COMTEX) -- According to a report form Acumen Research and Consulting, the Idiopathic Pulmonary Fibrosis Treatment Market size is expected to reach US$ 4.2 billion ...
- In the world of dentistry, Dr. Peter Dawson was a rock staron August 13, 2019 at 6:15 am
“All dentists know who Pete Dawson is,” Dr. Kim said. Dr. Dawson died July 27 of pulmonary fibrosis and congestive heart failure. He was 89. As a young man, the future dentist served his first ...
- Idiopathic Pulmonary Fibrosis Treatment Market Overviewon August 12, 2019 at 7:54 am
Idiopathic Pulmonary Fibrosis Treatment is a life-threatening condition of the lungs in which tissues becomes thickened, stiff, and scarred over a long period. The IPF treatment market is driven by ...
via Bing News