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. 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. 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. 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. 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. They next used a technique called high dimensionality reduction and spatial clustering (HDR-SC) to sort pixels with similar metabolite levels into clusters. 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. These are ready to use … for biological research.Ĭomplex 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. These are no longer tools being developed in an engineering or chemistry lab somewhere that are still waiting to be perfected. “We actually got some covid-19 lungs from a person that ended up passing away,” recalled Sun. ![]() 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. 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. A recently published study in Nature Communications suggests that glycogen could be an important therapeutic target. 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. 2 If clinicians are unable to find the cause of the fibrosis, they diagnose the patient with idiopathic pulmonary fibrosis (IPF).Ĭurrently, there are only two anti-fibrotic drugs endorsed by the Food and Drug Administration for the treatment of pulmonary fibrosis. ILDs with pulmonary fibrosis can result from genetic mutations, an underlying disease, or environmental exposure to microbes, smoke, or radiation. 1 Ultimately, pulmonary fibrosis results in the thickening of the alveolar walls, which limits oxygen uptake and causes difficulty breathing. 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. ![]() Many patients with ILDs develop pulmonary fibrosis, which is the gradual scarring of the lungs. Most people take breathing for granted, but patients with interstitial lung diseases (ILDs) remember its importance every time they struggle to take a breath.
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