Evaluation and Management of Pulmonary Hypertension in ...
Glycogen Metabolism May Play A Key Role In Pulmonary Fibrosis
Ramon Sun and his team use MALDI-MSI to investigate aberrant metabolism in diseases including pulmonary fibrosis.
Cameron Shedlock
Most people take breathing for granted, but patients with interstitial lung diseases (ILDs) remember its importance every time they struggle to take a breath. Many patients with ILDs develop pulmonary fibrosis, which is the gradual scarring of the lungs. This progressive and fatal process results from excessive extracellular matrix production and deposition by lung fibroblasts and myofibroblasts, where collagen, elastin, and N-linked glycans are the major components of the matrix.1 Ultimately, pulmonary fibrosis results in the thickening of the alveolar walls, which limits oxygen uptake and causes difficulty breathing. ILDs with pulmonary fibrosis can result from genetic mutations, an underlying disease, or environmental exposure to microbes, smoke, or radiation.2 If clinicians are unable to find the cause of the fibrosis, they diagnose the patient with idiopathic pulmonary fibrosis (IPF).
Currently, there are only two anti-fibrotic drugs endorsed by the Food and Drug Administration for the treatment of pulmonary fibrosis.3 Although both drugs slow the disease's progression, neither treatment can completely stop or reverse the lung damage, highlighting the need for novel therapeutics. A recently published study in Nature Communications suggests that glycogen could be an important therapeutic target.4
Ramon Sun, a biochemist at the University of Florida and corresponding author of the paper, studies metabolic pathways involved in diseases such as Alzheimer's disease, Ewing sarcoma, and lung cancer. When the covid pandemic shut down non-essential research, Sun was presented with the opportunity to study metabolic changes that occur during this infectious disease. "We actually got some covid-19 lungs from a person that ended up passing away," recalled Sun.
These are no longer tools being developed in an engineering or chemistry lab somewhere that are still waiting to be perfected. These are ready to use … for biological research. Ramon Sun, University of Florida
Complex carbohydrate metabolism is irregular in many human disorders, including neurodegeneration and some cancers, but scientists did not know if it was abnormal in patients with covid. Sun and his research team first scanned the lung tissue sections using matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry imaging (MALDI-MSI), which measured the metabolite abundance at individual pixels. They next used a technique called high dimensionality reduction and spatial clustering (HDR-SC) to sort pixels with similar metabolite levels into clusters. By comparing the clusters' locations to pathological regions of the lung, the researchers observed that three clusters corresponded exactly to the early-, mid-, and end-stage fibrotic regions of the SARS-CoV-2 infected lungs, indicating that complex carbohydrate metabolism is aberrant in these areas. To further investigate this abnormality, they analyzed the abundance of complex carbohydrates and uncovered that N-linked glycans and glycogen accumulated within the lungs' fibrotic regions.
Because patients with IPF have lung fibrosis, Sun wondered if complex carbohydrate metabolism was also altered in this condition. Using MALDI-MSI, they observed that glycogen- and N-linked glycan-rich areas corresponded to fibrotic regions, indicating that this carbohydrate signature could help clinicians identify fibrosis.
Ramon Sun and colleagues acquired MALDI mass spectrometry images like this one, which shows glucose 6-phosphate abundance in a genetically engineered mouse model of lung cancer.
Harrison Clark
The researchers next questioned whether glycogen metabolism is directly involved in scar formation, as glycogen breakdown in myofibroblast lysosomes could supply the cells with substrates for N-linked glycan production and deposition. They employed mouse models that lacked enzymes required for glycogen catabolism and induced lung injury through intratracheal administration of bleomycin, an antibiotic used to treat cancer, which causes inflammation that later progresses to fibrosis. Through MALDI-MSI analysis, the researchers found less N-linked glycan deposition and fibrosis in the lungs of mice unable to break down glycogen, which suggested that the degradation of glycogen was important for pulmonary fibrosis development.
"I think the ability to localize signals within a tissue and find these coordinated events across the tissue region and compare these in a disease, like pulmonary fibrosis where you have such regional heterogeneity, was very powerful," said Nicholas Banovich, a genomic scientist at the Translational Genomics Research Institute, who was not involved in the study. "I want to see these authors, as well as others in the field, continue to develop these imaging mass spectrometry approaches, and to see these platforms mature in the same way that we are starting to see the spatial transcriptomic platforms mature."
Sun is optimistic that this research could change the way that clinicians treat and diagnose pulmonary fibrosis. His team plans to find inhibitors targeting glycogen synthesis and degradation to develop into pulmonary fibrosis therapies. He also intends to create a spatial metabolomics-based protocol that could assist clinicians with pulmonary fibrosis diagnosis, saving them hours by pointing out regions that could be of interest. Additionally, Sun hopes that this paper inspires other researchers to employ spatial metabolomics techniques in their laboratories. "These are no longer tools being developed in an engineering or chemistry lab somewhere that are still waiting to be perfected. These are ready to use … for biological research," Sun said.
referencesKatie Price Joins Mum Amy In Pulmonary Fibrosis Campaign Saying 'no One's Ever Heard Of It – But It's Devastating'
KATIE Price has joined her mum Amy in an Action For Pulmonary Fibrosis campaign.
Former glamour model Katie, 45, is supporting the lung charity as they launch their hardest hitting campaign yet.
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Katie Price has joined her mum Amy in an Action For Pulmonary Fibrosis campaignCredit: InstagramAmy, 71, who lived with the condition before her recent lung transplant, has joined forces with her famous daughter for the good cause.
The campaign - called 'You Can't See What's Killing Me' - comes on the back of new stats revealing a staggering lack of awareness of this killer lung disease that's on the rise.
Amy said, "I know what it's like to live with pulmonary fibrosis - it's a horrible disease that robs you of your breath and life.
"We need to grab people's attention, so more people know what pulmonary fibrosis is.
"Our GPs and nurses at the surgeries require more training so they can recognise the symptoms of pulmonary fibrosis and not confuse it with asthma and other lung diseases.
"That's why I'm supporting Action for Pulmonary Fibrosis's campaign."
Katie added, "Mum's been amazing but it's been devastating having pulmonary fibrosis - for her and the whole family.
"When you say cancer everyone knows what it is but with pulmonary fibrosis nobody's ever heard of it.
GOODNIGHT JEAN
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oh hel!
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'SAD DAY'
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OOPS!
Emily Ratajkowski suffers embarrassing wardrobe malfunction at MTV VMAs"That's why I'm so passionate about more people knowing about it and supporting Action for Pulmonary Fibrosis and their hearmylungs.Com campaign this September."
The new stats reveal over three quarters of people with pulmonary fibrosis said their GP didn't tell them they might have pulmonary fibrosis before referring them to hospital, leaving patients unaware they're living with a fatal lung disease.
30% of people in the UK have never heard of pulmonary fibrosis, yet the average life expectancy for someone living with the disease is three-to-seven years. This is worse than many common cancers such as breast and prostate cancer.
Action for Pulmonary Fibrosis has developed a hard-hitting AI led campaign with the sound of pulmonary fibrosis to raise more awareness about this deadly disease.
The campaign invites people to scan a QR code and listen to the sound of Geoff who is living with deeply scarred lungs and hoping to receive a lung transplant.
Amy was diagnosed with idopathic pulmonary fibrosis in 2017.
As of 2023, she continues her ongoing health battle as her illness is terminal and there is no cure.
Katie's mum underwent a life-changing lung transplant last year and spent three months recovering at the hospital in Uxbridge, West London.
Symptoms of Idiopathic pulmonary fibrosis include shortness of breath, a persistent dry cough, tiredness, loss of appetite and weight loss, and rounded and swollen fingertips.
According to Action for Pulmonary Fibrosis, the transplant will improve her quality of life and help her live longer.
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Amy lived with the condition before her recent lung transplantCredit: Rex3
She's joined forces with her famous daughter for the good causeCredit: InstagramAmesbury Lion To Lead Pulmonary Fibrosis Walk
AMESBURY — The second annual New England Community Walk for the Pulmonary Fibrosis Foundation (PFF) will step off at Great Island Common, New Castle, N.H., on Sept. 23 at 9:30 a.M.
Amesbury Lions Club member John Massaua, who is afflicted with pulmonary fibrosis (PF), having been diagnosed in 2017 and currently is considered advanced stage, is co-leading the event for the New England Gills for PFF.
The New England Gills for PFF is an alliance cofounded by him, along with New Castle's Laurie Chandler, as a PF warrior-society of New Englanders for the expressed purpose of raising awareness and funds to support the PFF.
"I walk in service of others; I walk to raise awareness and funds for the Pulmonary Fibrosis Foundation 'ad majorem Dei gloriam,' because the foundation truly is a mover and a shaker in finding a cure for PF, probably not for me today, but in time, for others that will follow tomorrow," Massaua said.
The community of Amesbury is squarely behind Massaua with Amesbury Industrial Supply, Amesbury Dental and Amesbury's Gould Insurance sponsoring the event in part. Phat Cats Bistro and Kitchen Local are contributing in-kind for the day's planned silent auction. Numerous residents are making donations, many of whom will be walking as well.
"It is an honor to support John Massaua in raising awareness and funds for the Pulmonary Fibrosis Foundation; John's commitment to helping that organization find a cure for this debilitating disease is nothing short of remarkable," Amesbury Industrial Supply owner Greg Jardis said.
Jardis added his company valued being a part of the effort.
"We encourage other members of our community to come on out and participate in the day's festivities," he said.
Pulmonary fibrosis is a life-threatening disease that causes progressive scarring in the lungs. PF affects over 250,000 Americans annually and more than 50,000 new cases of PF are diagnosed each year.
According to the American Lung Association, 40,000 die annually from the disease, approximately as many as that die from breast cancer. The Pulmonary Fibrosis Foundation is the largest nonprofit organization dedicated to fighting PF.
PFF funds research, provides trusted educational materials, connects people with support groups and medical centers, and fosters a community so that no one need to go through the PF journey alone.
September is Pulmonary Fibrosis Awareness Month, and the New England Gills are urging patients, family and friends, caregivers, medical providers and interested individuals from all around the Seacoast and beyond to be amongst the walker-fundraisers.
The Gills will walk along the seaside green space and beach of New Castle's Great Island Common. Each walker can choose their own distance to stride along the scenic waterfront path. Following and during the Walk, an array of family-friendly activities (antique fire engine rides, face painting, supervised kids' games, a modern fire truck demonstration, and bubbles too) plus a special performance by North River Music will entertain guests of all ages.
For more information about the New England Community Walk and to register and/or donate, visit bit.Ly/GillsNECW4PFF.
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