Activation of Nrf2 in keratinocytes causes chloracne (MADISH)-like skin disease in mice

Publikationen: Beitrag in FachzeitschriftZeitschriftenaufsätzeForschung

Standard

Activation of Nrf2 in keratinocytes causes chloracne (MADISH)-like skin disease in mice. / Schäfer, Matthias; Willrodt, Ann-Helen; Kurinna, Svitlana; Link, Andrea S; Farwanah, Hany; Geusau, Alexandra; Gruber, Florian; Sorg, Olivier; Huebner, Aaron J; Roop, Dennis R; Sandhoff, Konrad; Saurat, Jean-Hilaire; Tschachler, Erwin; Schneider, Marlon R; Langbein, Lutz; Bloch, Wilhelm; Beer, Hans-Dietmar; Werner, Sabine.

in: EMBO molecular medicine, Jahrgang 6, Nr. 4, 01.04.2014, S. 442-457.

Publikationen: Beitrag in FachzeitschriftZeitschriftenaufsätzeForschung

Harvard

Schäfer, M, Willrodt, A-H, Kurinna, S, Link, AS, Farwanah, H, Geusau, A, Gruber, F, Sorg, O, Huebner, AJ, Roop, DR, Sandhoff, K, Saurat, J-H, Tschachler, E, Schneider, MR, Langbein, L, Bloch, W, Beer, H-D & Werner, S 2014, 'Activation of Nrf2 in keratinocytes causes chloracne (MADISH)-like skin disease in mice', EMBO molecular medicine, Jg. 6, Nr. 4, S. 442-457. https://doi.org/10.1002/emmm.201303281

APA

Schäfer, M., Willrodt, A-H., Kurinna, S., Link, A. S., Farwanah, H., Geusau, A., Gruber, F., Sorg, O., Huebner, A. J., Roop, D. R., Sandhoff, K., Saurat, J-H., Tschachler, E., Schneider, M. R., Langbein, L., Bloch, W., Beer, H-D., & Werner, S. (2014). Activation of Nrf2 in keratinocytes causes chloracne (MADISH)-like skin disease in mice. EMBO molecular medicine, 6(4), 442-457. https://doi.org/10.1002/emmm.201303281

Vancouver

Schäfer M, Willrodt A-H, Kurinna S, Link AS, Farwanah H, Geusau A et al. Activation of Nrf2 in keratinocytes causes chloracne (MADISH)-like skin disease in mice. EMBO molecular medicine. 2014 Apr 1;6(4):442-457. https://doi.org/10.1002/emmm.201303281

Bibtex

@article{156f10aca6e040818baf800f8b497404,
title = "Activation of Nrf2 in keratinocytes causes chloracne (MADISH)-like skin disease in mice",
abstract = "The transcription factor Nrf2 is a key regulator of the cellular stress response, and pharmacological Nrf2 activation is a promising strategy for skin protection and cancer prevention. We show here that prolonged Nrf2 activation in keratinocytes causes sebaceous gland enlargement and seborrhea in mice due to upregulation of the growth factor epigen, which we identified as a novel Nrf2 target. This was accompanied by thickening and hyperkeratosis of hair follicle infundibula. These abnormalities caused dilatation of infundibula, hair loss, and cyst development upon aging. Upregulation of epigen, secretory leukocyte peptidase inhibitor (Slpi), and small proline-rich protein 2d (Sprr2d) in hair follicles was identified as the likely cause of infundibular acanthosis, hyperkeratosis, and cyst formation. These alterations were highly reminiscent to the phenotype of chloracne/{"}metabolizing acquired dioxin-induced skin hamartomas{"} (MADISH) patients. Indeed, SLPI, SPRR2, and epigen were strongly expressed in cysts of MADISH patients and upregulated by dioxin in human keratinocytes in an NRF2-dependent manner. These results identify novel Nrf2 activities in the pilosebaceous unit and point to a role of NRF2 in MADISH pathogenesis.",
author = "Matthias Sch{\"a}fer and Ann-Helen Willrodt and Svitlana Kurinna and Link, {Andrea S} and Hany Farwanah and Alexandra Geusau and Florian Gruber and Olivier Sorg and Huebner, {Aaron J} and Roop, {Dennis R} and Konrad Sandhoff and Jean-Hilaire Saurat and Erwin Tschachler and Schneider, {Marlon R} and Lutz Langbein and Wilhelm Bloch and Hans-Dietmar Beer and Sabine Werner",
year = "2014",
month = apr,
day = "1",
doi = "10.1002/emmm.201303281",
language = "English",
volume = "6",
pages = "442--457",
journal = "EMBO molecular medicine",
issn = "1757-4676",
publisher = "Wiley-Blackwell",
number = "4",

}

RIS

TY - JOUR

T1 - Activation of Nrf2 in keratinocytes causes chloracne (MADISH)-like skin disease in mice

AU - Schäfer, Matthias

AU - Willrodt, Ann-Helen

AU - Kurinna, Svitlana

AU - Link, Andrea S

AU - Farwanah, Hany

AU - Geusau, Alexandra

AU - Gruber, Florian

AU - Sorg, Olivier

AU - Huebner, Aaron J

AU - Roop, Dennis R

AU - Sandhoff, Konrad

AU - Saurat, Jean-Hilaire

AU - Tschachler, Erwin

AU - Schneider, Marlon R

AU - Langbein, Lutz

AU - Bloch, Wilhelm

AU - Beer, Hans-Dietmar

AU - Werner, Sabine

PY - 2014/4/1

Y1 - 2014/4/1

N2 - The transcription factor Nrf2 is a key regulator of the cellular stress response, and pharmacological Nrf2 activation is a promising strategy for skin protection and cancer prevention. We show here that prolonged Nrf2 activation in keratinocytes causes sebaceous gland enlargement and seborrhea in mice due to upregulation of the growth factor epigen, which we identified as a novel Nrf2 target. This was accompanied by thickening and hyperkeratosis of hair follicle infundibula. These abnormalities caused dilatation of infundibula, hair loss, and cyst development upon aging. Upregulation of epigen, secretory leukocyte peptidase inhibitor (Slpi), and small proline-rich protein 2d (Sprr2d) in hair follicles was identified as the likely cause of infundibular acanthosis, hyperkeratosis, and cyst formation. These alterations were highly reminiscent to the phenotype of chloracne/"metabolizing acquired dioxin-induced skin hamartomas" (MADISH) patients. Indeed, SLPI, SPRR2, and epigen were strongly expressed in cysts of MADISH patients and upregulated by dioxin in human keratinocytes in an NRF2-dependent manner. These results identify novel Nrf2 activities in the pilosebaceous unit and point to a role of NRF2 in MADISH pathogenesis.

AB - The transcription factor Nrf2 is a key regulator of the cellular stress response, and pharmacological Nrf2 activation is a promising strategy for skin protection and cancer prevention. We show here that prolonged Nrf2 activation in keratinocytes causes sebaceous gland enlargement and seborrhea in mice due to upregulation of the growth factor epigen, which we identified as a novel Nrf2 target. This was accompanied by thickening and hyperkeratosis of hair follicle infundibula. These abnormalities caused dilatation of infundibula, hair loss, and cyst development upon aging. Upregulation of epigen, secretory leukocyte peptidase inhibitor (Slpi), and small proline-rich protein 2d (Sprr2d) in hair follicles was identified as the likely cause of infundibular acanthosis, hyperkeratosis, and cyst formation. These alterations were highly reminiscent to the phenotype of chloracne/"metabolizing acquired dioxin-induced skin hamartomas" (MADISH) patients. Indeed, SLPI, SPRR2, and epigen were strongly expressed in cysts of MADISH patients and upregulated by dioxin in human keratinocytes in an NRF2-dependent manner. These results identify novel Nrf2 activities in the pilosebaceous unit and point to a role of NRF2 in MADISH pathogenesis.

U2 - 10.1002/emmm.201303281

DO - 10.1002/emmm.201303281

M3 - Journal articles

C2 - 24503019

VL - 6

SP - 442

EP - 457

JO - EMBO molecular medicine

JF - EMBO molecular medicine

SN - 1757-4676

IS - 4

ER -

ID: 65196