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JCI Insight. 2022 Oct 11:e161870. doi: 10.1172/jci.insight.161870. Online ahead of print.


Rosacea is a chronic skin disorder characterized by abnormal neurovascular and inflammatory conditions on the central face. Despite increasing evidence suggests that rosacea is associated with metabolic disorders, the role of metabolism in rosacea pathogenesis remains unknown. Here, via targeted metabolomics approach, we characterized significantly altered metabolic signatures in rosacea patients, especially for amino acid-related metabolic pathways. Among these, glutamic acid and aspartic acid are highlighted and positively correlated with the disease severity in rosacea patients. We further demonstrated that glutamic acid and aspartic acid can facilitate the development of erythema and telangiectasia, typical features of rosacea, in the skin of mice. Mechanistically, glutamic acid and aspartic acid stimulate the production of vasodilation-related neuropeptides from peripheral neuron and keratinocytes, and induce the release of nitric oxide from endothelial cells and keratinocytes. Interestingly, we provided evidence showing that doxycycline can improve the symptoms of rosacea patients possibly by targeting amino acid metabolic pathway. These findings reveal that abnormal amino acid metabolism promotes neurovascular reactivity in rosacea, and raise the possibility of targeting dysregulated metabolism as a promising strategy for clinical treatment.

PMID:36219476 | DOI:10.1172/jci.insight.161870

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