ZEB2-transgene expression in the epidermis compromises the integrity of the epidermal barrier through the repression of different tight junction proteins

Marianthi N Tatari, Bram A De Craene, Bieke Soen, Joachim Taminau, Petra Vermassen, Steven Goossens, Katharina Haigh, Silvia Cazzola, Jo Lambert, Danny Huylebroeck, Jody Jonathan Haigh, Geert Berx

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Epithelial homeostasis within the epidermis is maintained by means of multiple cell-cell adhesion complexes such as adherens junctions, tight junctions, gap junctions, and desmosomes. These complexes co-operate in the formation and the regulation of the epidermal barrier. Disruption of the epidermal barrier through the deregulation of the above complexes is the cause behind a number of skin disorders such as psoriasis, dermatitis, keratosis, and others. During epithelial-to-mesenchymal transition (EMT), epithelial cells lose their adhesive capacities and gain mesenchymal properties. ZEB transcription factors are key inducers of EMT. In order to gain a better understanding of the functional role of ZEB2 in epidermal homeostasis, we generated a mouse model with conditional overexpression of Zeb2 in the epidermis. Our analysis revealed that Zeb2 expression in the epidermis leads to hyperproliferation due to the combined downregulation of different tight junction proteins compromising the epidermal barrier. Using two epidermis-specific in vivo models and in vitro promoter assays, we identified occludin as a new Zeb2 target gene. Immunohistological analysis performed on human skin biopsies covering various pathogeneses revealed ZEB2 expression in the epidermis of pemphigus vulgaris. Collectively, our data support the notion for a potential role of ZEB2 in intracellular signaling of this disease. ? 2014 Springer.
Original languageEnglish
Pages (from-to)3599-3609
Number of pages11
JournalCellular and Molecular Life Sciences
Volume71
Issue number18
DOIs
Publication statusPublished - 2014

Cite this

Tatari, Marianthi N ; De Craene, Bram A ; Soen, Bieke ; Taminau, Joachim ; Vermassen, Petra ; Goossens, Steven ; Haigh, Katharina ; Cazzola, Silvia ; Lambert, Jo ; Huylebroeck, Danny ; Haigh, Jody Jonathan ; Berx, Geert. / ZEB2-transgene expression in the epidermis compromises the integrity of the epidermal barrier through the repression of different tight junction proteins. In: Cellular and Molecular Life Sciences. 2014 ; Vol. 71, No. 18. pp. 3599-3609.
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abstract = "Epithelial homeostasis within the epidermis is maintained by means of multiple cell-cell adhesion complexes such as adherens junctions, tight junctions, gap junctions, and desmosomes. These complexes co-operate in the formation and the regulation of the epidermal barrier. Disruption of the epidermal barrier through the deregulation of the above complexes is the cause behind a number of skin disorders such as psoriasis, dermatitis, keratosis, and others. During epithelial-to-mesenchymal transition (EMT), epithelial cells lose their adhesive capacities and gain mesenchymal properties. ZEB transcription factors are key inducers of EMT. In order to gain a better understanding of the functional role of ZEB2 in epidermal homeostasis, we generated a mouse model with conditional overexpression of Zeb2 in the epidermis. Our analysis revealed that Zeb2 expression in the epidermis leads to hyperproliferation due to the combined downregulation of different tight junction proteins compromising the epidermal barrier. Using two epidermis-specific in vivo models and in vitro promoter assays, we identified occludin as a new Zeb2 target gene. Immunohistological analysis performed on human skin biopsies covering various pathogeneses revealed ZEB2 expression in the epidermis of pemphigus vulgaris. Collectively, our data support the notion for a potential role of ZEB2 in intracellular signaling of this disease. ? 2014 Springer.",
author = "Tatari, {Marianthi N} and {De Craene}, {Bram A} and Bieke Soen and Joachim Taminau and Petra Vermassen and Steven Goossens and Katharina Haigh and Silvia Cazzola and Jo Lambert and Danny Huylebroeck and Haigh, {Jody Jonathan} and Geert Berx",
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Tatari, MN, De Craene, BA, Soen, B, Taminau, J, Vermassen, P, Goossens, S, Haigh, K, Cazzola, S, Lambert, J, Huylebroeck, D, Haigh, JJ & Berx, G 2014, 'ZEB2-transgene expression in the epidermis compromises the integrity of the epidermal barrier through the repression of different tight junction proteins' Cellular and Molecular Life Sciences, vol. 71, no. 18, pp. 3599-3609. https://doi.org/10.1007/s00018-014-1589-0

ZEB2-transgene expression in the epidermis compromises the integrity of the epidermal barrier through the repression of different tight junction proteins. / Tatari, Marianthi N; De Craene, Bram A; Soen, Bieke; Taminau, Joachim; Vermassen, Petra; Goossens, Steven; Haigh, Katharina; Cazzola, Silvia; Lambert, Jo; Huylebroeck, Danny; Haigh, Jody Jonathan; Berx, Geert.

In: Cellular and Molecular Life Sciences, Vol. 71, No. 18, 2014, p. 3599-3609.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - ZEB2-transgene expression in the epidermis compromises the integrity of the epidermal barrier through the repression of different tight junction proteins

AU - Tatari, Marianthi N

AU - De Craene, Bram A

AU - Soen, Bieke

AU - Taminau, Joachim

AU - Vermassen, Petra

AU - Goossens, Steven

AU - Haigh, Katharina

AU - Cazzola, Silvia

AU - Lambert, Jo

AU - Huylebroeck, Danny

AU - Haigh, Jody Jonathan

AU - Berx, Geert

PY - 2014

Y1 - 2014

N2 - Epithelial homeostasis within the epidermis is maintained by means of multiple cell-cell adhesion complexes such as adherens junctions, tight junctions, gap junctions, and desmosomes. These complexes co-operate in the formation and the regulation of the epidermal barrier. Disruption of the epidermal barrier through the deregulation of the above complexes is the cause behind a number of skin disorders such as psoriasis, dermatitis, keratosis, and others. During epithelial-to-mesenchymal transition (EMT), epithelial cells lose their adhesive capacities and gain mesenchymal properties. ZEB transcription factors are key inducers of EMT. In order to gain a better understanding of the functional role of ZEB2 in epidermal homeostasis, we generated a mouse model with conditional overexpression of Zeb2 in the epidermis. Our analysis revealed that Zeb2 expression in the epidermis leads to hyperproliferation due to the combined downregulation of different tight junction proteins compromising the epidermal barrier. Using two epidermis-specific in vivo models and in vitro promoter assays, we identified occludin as a new Zeb2 target gene. Immunohistological analysis performed on human skin biopsies covering various pathogeneses revealed ZEB2 expression in the epidermis of pemphigus vulgaris. Collectively, our data support the notion for a potential role of ZEB2 in intracellular signaling of this disease. ? 2014 Springer.

AB - Epithelial homeostasis within the epidermis is maintained by means of multiple cell-cell adhesion complexes such as adherens junctions, tight junctions, gap junctions, and desmosomes. These complexes co-operate in the formation and the regulation of the epidermal barrier. Disruption of the epidermal barrier through the deregulation of the above complexes is the cause behind a number of skin disorders such as psoriasis, dermatitis, keratosis, and others. During epithelial-to-mesenchymal transition (EMT), epithelial cells lose their adhesive capacities and gain mesenchymal properties. ZEB transcription factors are key inducers of EMT. In order to gain a better understanding of the functional role of ZEB2 in epidermal homeostasis, we generated a mouse model with conditional overexpression of Zeb2 in the epidermis. Our analysis revealed that Zeb2 expression in the epidermis leads to hyperproliferation due to the combined downregulation of different tight junction proteins compromising the epidermal barrier. Using two epidermis-specific in vivo models and in vitro promoter assays, we identified occludin as a new Zeb2 target gene. Immunohistological analysis performed on human skin biopsies covering various pathogeneses revealed ZEB2 expression in the epidermis of pemphigus vulgaris. Collectively, our data support the notion for a potential role of ZEB2 in intracellular signaling of this disease. ? 2014 Springer.

UR - http://link.springer.com/article/10.1007%2Fs00018-014-1589-0

U2 - 10.1007/s00018-014-1589-0

DO - 10.1007/s00018-014-1589-0

M3 - Article

VL - 71

SP - 3599

EP - 3609

JO - Cellular and Molecular Life Sciences

JF - Cellular and Molecular Life Sciences

SN - 1420-682X

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