Distribution and Expression of Non-Neuronal Transient Receptor Potential (TRPV) Ion Channels in Rosacea

Abstract

Rosacea is a frequent chronic inflammatory skin disease of unknown etiology. Because early rosacea reveals all characteristics of neurogenic inflammation, a central role of sensory nerves in its pathophysiology has been discussed. Neuroinflammatory mediators and their receptors involved in rosacea are poorly defined. Good candidates may be transient receptor potential (TRP) ion channels of vanilloid type (TRPV), which can be activated by many trigger factors of rosacea. Interestingly, TRPV2, TRPV3, and TRPV4 are expressed by both neuronal and non-neuronal cells. Here, we analyzed the expression and distribution of TRPV receptors in the various subtypes of rosacea on non-neuronal cells using immunohistochemistry, morphometry, double immunoflourescence, and quantitative real-time PCR (qRT-PCR) as compared with healthy skin and lupus erythematosus. Our results show that dermal immunolabeling of TRPV2 and TRPV3 and gene expression of TRPV1 is significantly increased in erythematotelangiectatic rosacea (ETR). Papulopustular rosacea (PPR) displayed an enhanced immunoreactivity for TRPV2, TRPV4, and also of TRPV2 gene expression. In phymatous rosacea (PhR)-affected skin, dermal immunostaining of TRPV3 and TRPV4 and gene expression of TRPV1 and TRPV3 was enhanced, whereas epidermal TRPV2 staining was decreased. Thus, dysregulation of TRPV channels also expressed by non-neuronal cells may be critically involved in the initiation and/or development of rosacea. TRP ion channels may be targets for the treatment of rosacea.

Augmented supraorbital skin sympathetic nerve activity responses to symptom trigger events in rosacea patients

“…Local heat stimulates TRPV receptors on warm sensory afferents. TRPV subtypes 1-4 are upregulated in affected skin in erythematotelangiectatic rosacea (Sulk et al 2012). Despite this, we did not observe a difference in initial peaks, indicating intact axon reflexes in rosacea.…”

The Ca2+-Permeable Cation Transient Receptor Potential TRPV3 Channel: An Emerging Pivotal Target for Itch and Skin Diseases

“…TRPV3 expression is upregulated in dermal cells isolated from rosacea, a common chronic inflammatory skin disease, further supporting the important role of the TRPV3 channel in cutaneous inflammation (Sulk et al, 2012).…”

TRPV3 mutants causing Olmsted Syndrome induce impaired cell adhesion and nonfunctional lysosomes

“…[29][30][31] In fact, expression of TRPV3 is more in skin than in sensory neurons. 20,29 TRPV3 also regulates hair follicle, hair growth and keratinocyte functions.…”