Rosacea Is Characterized by a Profoundly Diminished Skin Barrier

Abstract

Rosacea is a common chronic inflammation of sebaceous glanderich 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 patients with rosacea. Thus, we aimed to investigate the barrier alterations in papulopustular rosacea samples compared with healthy sebaceous glanderich skin, using RNA sequencing analysis (n ¼ 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 papulopustular rosacea samples compared with sebaceous glanderich skin, including the cornified envelope and intercellular lipid lamellae formation, desmosome and tight junction organizations, barrier alarmins, and antimicrobial peptides. Moreover, the barrier damage in papulopustular rosacea was unexpectedly similar to atopic dermatitis; 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 papulopustular rosacea at the molecular level, which highlight the importance of barrier repair therapies for rosacea.

Keratinocyte-Immune Cell Crosstalk in a STAT1-Mediated Pathway: Novel Insights Into Rosacea Pathogenesis

“…We found that cornification and formation of the cornified envelope in ETR and PPR indicated epidermal dysfunction (skin barrier) as an early phase of rosacea. Previous study of the PPR subtype found it characterized by a profoundly diminished skin barrier ( 18 ); our results further support the prominent permeability barrier alterations in ETR at the molecular level, which highlight the diminished skin barrier as a potential initiator of rosacea.…”

“…Previous whole-skin transcriptome analysis revealed that Th1/Th17 polarized inflammation and macrophage infiltration were hallmarks in ETR, PPR and PHR subtypes ( 6 ), and separated signals of immune and keratinization gene expression in PPR ( 17 ). In addition, prominent permeability barrier alterations had also been descried in PPR via whole-skin RNA sequencing analysis ( 18 ). In the present study, through both whole-skin and epidermal transcriptome analysis, we characterized the atlas of transcriptomic profiles indicating the site-specific gene signatures and epidermal homeostasis for central facial skin.…”

Contact sensitization to cosmetic series of allergens in female patients with rosacea: A prospective controlled study in China

“…The so‐called sensitive skin in rosacea patients is so far ill‐defined and less studied. It can be partially explained by the damaged epidermal barrier, which allows increased penetration of irritants and allergens 17 . Threshold for contact reaction is also reduced by epidermal inflammation and increased irritability of cutaneous nerve endings 18 …”

Adipokines in the Skin and in Dermatological Diseases

“…As SERPINs are known to interact with kallikreins, which are important regulators of the immune barrier alteration and skin desquamation, they might be involved in modifying the physiological structures of the epidermis, which can lead to the typical clinical signs in rosacea [209][210][211]. Epidermal LCN2 levels were also significantly higher in papulopustular rosacea compared with controls and this expression level was strongly associated with the levels of permeability barrier structural components [212]. Leptin, adiponectin, resistin, SERPINE1 and visfatin were also detectable in the SGs of rosacea-involved skin, suggesting that through the secretion of these adipokines, SGs may contribute to the development of the characteristic inflammatory milieu in rosacea [101].…”