Claudin reduction may relate to an impaired skin barrier in rosacea

Abstract

Rosacea is a chronic inflammatory skin disorder whose pathophysiological mechanism remains largely unknown. Although recent studies have revealed the hypersensitivity of the skin towards chemical, thermal and biological stimuli, there is no direct molecular evidence suggesting the skin barrier is impaired in rosacea. In this study, we demonstrated that the mRNA levels of most claudins (CLDN), the main components of tight junctions determining the major barrier of the paracellular pathway between epithelial cells, were lowered in lesional skin of rosacea patients, especially with erythematotelangiectatic (ETR) and papulopustular (PPR) subtypes. Immunohistochemical analysis showed a significant decrease in the expression of CLDN1, CLDN3, CLDN4 and CLDN5 in the epidermis of ETR and PPR patients. However, the expression of other skin barrier genes, such as filaggrin, loricrin and keratin 10, was not altered. In vitro, various rosacea trigger factors reduced the protein levels of CLDN1, CLDN3 and CLDN5 in keratinocytes. Taken together, our results demonstrate a significant decrease in the expression of CLDN rather than other skin barrier genes, which may be associated with an impaired skin barrier responsible for the development of rosacea.

Rosacea Is Characterized by a Profoundly Diminished Skin Barrier

“…They also studied the tight junction protein CLDN1 and could detect significantly lower gene expression and protein levels of CLDN1 in PPR samples compared with controls, in agreement with our results. Regarding the mRNA levels of KRT10 and LOR, the authors of this study did not find significant differences when comparing PPR to controls, and protein levels were not assessed (Deng et al, 2019). The expression of KLK5 in rosacea has been studied previously by another workgroup, and its mRNA and protein levels were demonstrated to be significantly increased, in parallel with elevated enzyme activity; however, the authors did not specify which rosacea subtype had been assessed (Morizane et al, 2010;Yamasaki and Gallo, 2011).…”

“…In this previous study, the authors focused on examining the immunological characteristics of different rosacea subtypes, and no data were published on barrier components (Buhl et al, 2015). Another study, performed by Deng et al, focused on mRNA expression levels of cornified envelope components, including KRT10, FLG, and LOR in different rosacea subtypes (Deng et al, 2019). They also studied the tight junction protein CLDN1 and could detect significantly lower gene expression and protein levels of CLDN1 in PPR samples compared with controls, in agreement with our results.…”

<p>A Preliminary Clinical Evaluation of a Topical Product for Reducing Slight Rosacea Imperfections</p>

“…Some studies have proven that alterations of skin barrier may promote skin disorders and defective expression of proteins involved in the correct setup of the skin barrier has been reported during rosacea progression. 5,13 An altered barrier function is mainly visible by increased water loss, also promoted by the altered epidermal vascularization. 5 Several clinical parameters have been used to assess the effect of Serum BK46 on symptom severity, including both instrumental techniques and clinical assessment to evaluate skin hydration, water loss, skin redness, erythema, and telangiectasias.…”

How Probiotics Affect the Microbiota

“…As proposed in the epimmunome theory, the barrier status is fundamental for skin defense and immune orientation (Swamy et al, 2010). Skin immune conditions, such as rosacea, acne, and atopy, are associated with skin barrier disruption, and the restoration of the barrier is associated with an improvement in clinical outcomes (Deng et al, 2019). A local application of the probiotics L. bulgaricus, L. acidophilus, or L. plantarum improves the outcome of acne by reducing skin colonization by Cutibacterium acnes (Bowe and Logan, 2011;Muizzuddin et al, 2012).…”