Impaired tight junctions obstruct stratum corneum formation by altering polar lipid and profilaggrin processing

Tobisawa, Yuki; Komiya, Aya; Kusaka, Ayumi; Kuze, Tetsuya; Sugiyama, Yoshinori; Inoue, Shintaro

doi:10.1016/j.jdermsci.2012.11.595

Cited by 61 publications

(53 citation statements)

References 55 publications

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“…Conversely, low expression of claudin-1 as observed in AD may be associated with deficient Notch signalling. Disruption of TJ barriers with an inhibitory peptide against specific claudins resulted in impaired maturation of lamellae structures, deficient profilaggrin processing as well as decreased non-polar barrier lipids (46). Claudin-1 deficient mice exhibited increased TEWL, altered SC ceramide composition and disturbed filaggrin processing (47).…”

Section: Tight Junctionsmentioning

confidence: 99%

The Potential Role of Impaired Notch Signalling in Atopic Dermatitis

Melnik

2015

Acta Derm Venerol

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This review presents recent evidence of impaired Notch signalling in atopic dermatitis (AD), which is proposed to represent the "a-topic" defect linking both epidermal and immunological barrier dysfunctions in AD. AD epidermis exhibits a marked deficiency of Notch receptors. Mouse models with genetically suppressed Notch signalling exhibit dry skin, signs of scratching, skin barrier abnormalities, increased transepidermal water loss and TH2 cell-mediated immunological changes closely resembling human AD. Notch signals are critically involved in the differentiation of regulatory T cells, in the feedback inhibition of activated innate immunity, in late epidermal differentiation associated with filaggrin- and stratum corneum barrier lipid processing. Most importantly, Notch deficiency induces keratinocyte-mediated release of thymic stromal lymphopoietin (TSLP). TSLP promotes TH2 cell-driven immune responses associated with enhanced production of interleukin (IL)-4 and IL-31. Both TSLP and IL-31 stimulate sensory cutaneous neurons involved in the induction of itch. Notably, Notch1 is a repressor of activator protein-1 (AP-1), which is upregulated in AD epidermis. Without Notch-mediated suppression of AP-1 this transcription factor promotes excess expression of TH2 cell-related cytokines. Impaired Notch signalling negatively affects the homeostasis of aquaporin 3 and of the tight junction component claudin-1, thus explains disturbed skin barrier function with increased transepidermal water loss and Staphylococcus aureus colonisation as well as increased cutaneous susceptibility for viral infections. Thus, accumulating evidence links deficient Notch signalling to key pathological features of AD.

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Section: Tight Junctionsmentioning

confidence: 99%

The Potential Role of Impaired Notch Signalling in Atopic Dermatitis

Melnik

2015

Acta Derm Venerol

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“…In a recent study, patients with AD demonstrated a defect in TJ barrier function and composition 26. Furthermore, Yuki et al27 reported that impaired TJ barriers affect polar lipids and profilaggrin processing by disturbing the pH of the SC. Based on these reports, we assume that decreased TJ components in lesional AD promote epicutaneous penetration of allergens, including the house dust mite antigen, which leads to the increased possibility of developing systemic allergy or atopic march.…”

Section: Introductionmentioning

confidence: 99%

Epidermal Permeability Barrier Defects and Barrier Repair Therapy in Atopic Dermatitis

Lee

2014

Allergy Asthma Immunol Res

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Atopic dermatitis (AD) is a multifactorial inflammatory skin disease perpetuated by gene-environmental interactions and which is characterized by genetic barrier defects and allergic inflammation. Recent studies demonstrate an important role for the epidermal permeability barrier in AD that is closely related to chronic immune activation in the skin during systemic allergic reactions. Moreover, acquired stressors (e.g., Staphylococcus aureus infection) to the skin barrier may also initiate inflammation in AD. Many studies involving patients with AD revealed that defective skin barriers combined with abnormal immune responses might contribute to the pathophysiology of AD, supporting the outside-inside hypothesis. In this review, we discuss the recent advances in human and animal models, focusing on the defects of the epidermal permeability barrier, its immunologic role and barrier repair therapy in AD.

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“…Therefore, it can be speculated that chitosan would enhance the contact of the LMs with the stratum corneum and hence the skin delivery of the encapsulated drug. With regard to the cellular tight junctions, their occurrence has been restricted to the epidermal region beneath the stratum corneum [50,51], although in one study their presence in the deepest stratum corneum layers has been suggested [52]. Therefore, the mechanism based on transient opening of tight junctions should not be involved in the increased stratum corneum uptake of resveratrol promoted by the chitosan-coated LMs.…”

Section: Discussionmentioning

confidence: 99%