Rosacea is Characterized by a Profoundly Diminished Skin Barrier.

Abstract Rosacea is a common, chronic inflammation of sebaceous gland-rich facial skin characterized by severe skin dryness, elevated pH, transepidermal water loss, and decreased hydration levels. Until now, there has been no thorough molecular analysis of permeability barrier alterations in the skin of rosacea patients. Thus, we aimed to investigate the barrier alterations in papulopustular rosacea (PPR) samples compared to healthy sebaceous gland-rich (SGR) skin, using RNASeq analysis (n=8). Pathway analyses by Cytoscape ClueGo revealed 15 significantly enriched pathways related to skin barrier formation. RT-PCR and immunohistochemistry were used to validate the pathway analyses. The results showed significant alterations in barrier components in PPR samples compared to SGR, including the cornified envelope and intercellular lipid lamellae formation, desmosome and tight junction organizations, barrier alarmins, and antimicrobial peptides. Moreover, the barrier damage in PPR was unexpectedly similar to atopic dermatitis (AD); this similarity was confirmed by immunofluorescent staining. In summary, besides the well-known dysregulation of immunological, vascular, and neurological functions, we demonstrated prominent permeability barrier alterations in PPR at the molecular level, which highlight the importance of barrier repair therapies for rosacea.