New research finds connection: Inflammation, metabolism and scleroderma scarring
Study finds NAD+ break down leads to multi organ scarring, providing now a previously undiscovered pathogenic role of the enzyme CD38 in disease scarring.
Scleroderma, a chronic and currently incurable orphan disease where tissue injury causes potentially lethal skin and lung scarring, remains poorly understood.
However, the defining characteristic of systemic sclerosis, the most serious form of scleroderma, is irreversible and progressive scarring that affects the skin and internal organs.
Published in iScience, Michigan Medicine’s Scleroderma Program and the rheumatology and dermatology departments partnered with the Northwestern Scleroderma Program in Chicago and Mayo Clinic to investigate the causes of disabling scarring, using human patient samples, preclinical mouse models and explanted human skin.
“We found that scleroderma inflammation dramatically increases CD38, an enzyme that normally breaks down a metabolic nutrient, NAD+. When NAD+ levels decrease, tissue injury becomes chronic and progresses to scar formation rather than to healthy repair,” says study author John Varga, M.D., division chief of rheumatology at Michigan Medicine.
According to the study, treatments that prevented NAD+ reduction in the mice, whether by boosting the levels of the nutrient genetically or pharmacologically, prevented scarring in the skin, lungs and abdominal wall.
“This is one of the first studies to find a relationship between CD38 and scleroderma, as well as the linking between inflammation and metabolism to skin and organ scarring,” says study author Johann Gudjonsson, M.D. Ph.D., a dermatologist at Michigan Medicine.
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