Up-regulation of Notch-1 in psoriasis: an immunohistochemical study

Abdou, Asmaa Gaber; Maraee, Alaa Hassan; Sharaf, Amany Youssef; Elnaidany, Nada Farag

doi:10.1016/j.anndiagpath.2011.09.005

Cited by 25 publications

(24 citation statements)

References 22 publications

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“…This is supported by in vitro studies showing that Notch‐1 is associated with keratinocyte maturity and cell differentiation . The expression of Notch‐1, DLL‐4 and Hrt‐1 in psoriasis is consistent with previous studies showing expression localized to the vasculature and lining layer regions of the PsA synovium . Furthermore, Notch‐1 has been shown to mediate TNF α ‐induced synoviocyte proliferation in inflammatory arthritis , suggesting a role for Notch in promoting proliferation of the synovium and invasion of adjacent cartilage.…”

Section: Discussionsupporting

confidence: 90%

“…In this study, we demonstrate increased Notch‐1, DLL‐4 and Hrt‐1 expression in psoriasis lesional skin compared with non‐lesional skin, with highest expression observed in the vascular regions. Notch‐1 expression has been demonstrated in psoriasis skin biopsies ; however, this is the first study to demonstrate expression of DLL‐4 and Hrt‐1. Targeted disruption of Notch signalling components can result in embryonic lethality, defects in angiogenic vascular remodelling, abnormalities in vessel structure, branching and patterning and dysfunctional vascular tip versus stalk cell development .…”

Section: Discussionmentioning

confidence: 69%

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Notch‐1 mediates endothelial cell activation and invasion in psoriasis

Rooney¹,

Connolly²,

Gao³

et al. 2014

Experimental Dermatology

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Notch receptor-ligand interactions are critical for cell proliferation, differentiation and survival; however, the role of Notch signalling in psoriasis remains to be elucidated. Serum amyloid A (A-SAA) is an acute-phase protein with cytokine-like properties, regulates cell survival pathways and is implicated in many inflammatory conditions. To examine the role of Notch-1 signalling in the pathogenesis of psoriasis, Notch-1, DLL-4, Jagged-1, Hrt-1/Hrt-2, A-SAA, Factor VIII and vascular endothelial growth factor (VEGF) mRNA and/or protein expression in psoriasis skin biopsies, serum and dHMVEC were assessed by immunohistology, dual-immunofluorescence, real-time PCR, ELISA and Western blotting. A-SAA-induced angiogenesis and invasion in the presence of Notch-1 siRNA was assessed by matrigel tube formation assays and Transwell invasion assay. Increased Notch-1, its ligand DLL-4 and Hrt-1 expression were demonstrated in lesional skin compared with non-lesional skin, with greatest expression observed in the dermal vasculature (P < 0.05). Dual-immunofluorescent staining demonstrated co-localization of Notch-1 to endothelial cell marker Factor VIII. A significant increase in A-SAA levels was demonstrated in psoriasis serum compared with healthy control serum (P < 0.05), and A-SAA expression was higher in lesional skin compared with non-lesional. In dHMVEC, A-SAA significantly induced Jagged-1, Hrt-1 and VEGF mRNA expression (P < 0.05) and activated Notch-1 IC indicative of transcriptional regulation. In contrast, A-SAA significantly inhibited DLL-4 mRNA expression (P < 0.05). Finally A-SAA-induced angiogenesis and invasion were inhibited by Notch-1 siRNA (P < 0.05). Notch receptor-ligand interactions mediate vascular dysfunction in psoriasis and may represent a potential therapeutic target.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 69%

Notch‐1 mediates endothelial cell activation and invasion in psoriasis

Rooney¹,

Connolly²,

Gao³

et al. 2014

Experimental Dermatology

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“…Notch deficiency appears to be a specific feature of AD as epidermal Notch expression is increased in other inflammatory skin diseases such as psoriasis and lichen planus (20,22). Loss-of-function mutation of ADAM17 in a sister and brother resulted in eczematous scaly skin prone to S. aureus infection (23).…”

Section: Notch Signallingmentioning

confidence: 98%

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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“…Notch proteins comprise a family of four type 1 transmembrane receptors that include four genes (Notch1, 2, 3, and 4), with abnormalities in organ development and adult homeostasis reported in cases with mutations in these genes [1, 25]. Notch ligands in mammals include Delta-like 1, 3, and 4 and Jagged-1 and -2.…”

Section: Introductionmentioning

confidence: 99%

Notch Signaling May Be Involved in the Abnormal Differentiation of Epidermal Keratinocytes in Psoriasis

Ota

Takekoshi

Takagi

et al. 2014

Acta Histochem. Cytochem.

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Localization of each keratin isoform differs among epidermal layers. Proliferating basal cells synthesize keratin 14 (K14) and suprabasal cells express keratin 10 (K10) in normal skin. Notch signaling is essential for keratinocyte differentiation. Notch1 is expressed in all epidermal layers, Notch2 in the basal cell layer and Notch3 in basal cell and spinous cell layers in normal epidermis. It has been poorly elucidated how localization and expression levels of Notch molecules are related to epidermal molecular markers K10 and K14 in psoriatic skin with abnormal differentiation of epidermal tissue. This study aimed to investigate the relationship between abnormal differentiation of epidermal cells in psoriatic skin and expression of Notch molecules. We investigated keratins (K14 and K10) and Notches (1, 2, 3 and 4) using immunohistochemistry in psoriatic skin (n=30) and normal skin (n=10). In normal skin, K14 and K10 were discretely observed in the basal cell layer and suprabasal layer, respectively. In psoriatic skin, K14 was expressed in the pan epidermal layer while it and K10 were co-expressed in some middle suprabasal layer cells. Notch1, 2, 3, and 4 localized in all epidermal layers in normal skin. In psoriatic skin, Notch1, 2, and 4 mainly localized in suprabasilar layers and Notch3 is lacalized in pan epidermal, suprabasilar, and basilar layers. Protein and mRNA of Notch1, 2, and 3 isoforms decreased in psoriatic epidermis compared with normal epidermis. These data suggest that decrements in these Notch molecules might cause aberrant expression of K10 and K14 leading to anomalous differentiation of the epidermis in psoriatic lesions.

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Up-regulation of Notch-1 in psoriasis: an immunohistochemical study

Cited by 25 publications

References 22 publications

Notch‐1 mediates endothelial cell activation and invasion in psoriasis

Notch‐1 mediates endothelial cell activation and invasion in psoriasis

The Potential Role of Impaired Notch Signalling in Atopic Dermatitis

Notch Signaling May Be Involved in the Abnormal Differentiation of Epidermal Keratinocytes in Psoriasis

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