%20involves%20fibrosis%20in%20multiple%20organs,%20but%20its%20cause%20is%20not%20fully%20understood.%20NAD+%20decline%20with%20age%20and%20disease,%20often%20due%20to%20increased%20CD38%20activity%20(an%20NADase),%20ma...){kind=link}
Counteracting CD38-Induced NAD+ Depletion Reduces Multiple Organ Fibrosis: Preclinical Findings
Synopsis
Systemic sclerosis (SSc) involves fibrosis in multiple organs, but its cause is not fully understood. NAD+ decline with age and disease, often due to increased CD38 activity (an NADase), may contribute. Researchers found CD38 levels were higher in skin of SSc patients, correlating with fibrosis severity, while NAD+ synthesis enzyme levels were unchanged. In mice, reducing CD38 genetically or with drugs, or boosting NAD+ with precursors, protected against fibrosis in skin, lungs, and peritoneum. Mechanistically, CD38 lowered NAD+ and sirtuin activity, increasing fibrotic responses, while inhibiting CD38 had the opposite effect. Thus, CD38-driven NAD+ loss is a key fibrosis driver and a potential target for SSc therapy.
Journal
iScience