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J Invest Dermatol. 2023 Jul 10:S0022-202X(23)02408-9. doi: 10.1016/j.jid.2023.05.028. Online ahead of print.

ABSTRACT

Recent efforts have described the transcriptomic landscape of rosacea. However, little is known about its proteomic characteristics. In this study, the proteome and phosphoproteome of lesional skin [LS], paired nonlesional skin [NS] and healthy skin (HS) were analysed by LC‒MS/MS. The molecular characteristics and potential pathogenic mechanism of rosacea were demonstrated by integrating the proteome, phosphoproteome and previous transcriptome. The proteomic data revealed a significant upregulation of inflammation- and axon extension-related proteins in LS and NS versus HS, implying an inflammatory and nerve-hypersensitive microenvironment in rosacea skin. Of these, axon-related proteins (DPYSL2 and DBNL) were correlated with the CEA score, and neutrophil-related proteins (ELANE and S100A family) were correlated with the IGA score. Moreover, comorbidity-related proteins were differentially expressed in rosacea; of these, α-synuclein was positively correlated with CEA score, implying a potential correlation between rosacea and comorbidities. Subsequently, the integrated proteome and transcriptome demonstrated consistent immune disturbances at both the transcriptional and protein levels. The integrative analysis of the proteome and phosphoproteome revealed the key TF network and kinase network that drive the dysregulation of immunity and vasculature in rosacea. In conclusion, our multiomics analysis enables more comprehensive insight into rosacea and offers an opportunity for novel treatment strategies.

PMID:37437773 | DOI:10.1016/j.jid.2023.05.028

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