Cargando…

ZFP750 affects the cutaneous barrier through regulating lipid metabolism

An essential function of the epidermis is to provide a physical barrier that prevents the loss of water. Essential mediators of this barrier function include ceramides, cholesterol, and very long chain fatty acids, and their alteration causes human pathologies, including psoriasis and atopic dermati...

Descripción completa

Detalles Bibliográficos
Autores principales: Butera, Alessio, Agostini, Massimiliano, Cassandri, Matteo, De Nicola, Francesca, Fanciulli, Maurizio, D’Ambrosio, Lorenzo, Falasca, Laura, Nardacci, Roberta, Wang, Lu, Piacentini, Mauro, Knight, Richard A., Jia, Wei, Sun, Qiang, Shi, Yufang, Wang, Ying, Candi, Eleonora, Melino, Gerry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10146900/
https://www.ncbi.nlm.nih.gov/pubmed/37115925
http://dx.doi.org/10.1126/sciadv.adg5423
_version_ 1785034689286766592
author Butera, Alessio
Agostini, Massimiliano
Cassandri, Matteo
De Nicola, Francesca
Fanciulli, Maurizio
D’Ambrosio, Lorenzo
Falasca, Laura
Nardacci, Roberta
Wang, Lu
Piacentini, Mauro
Knight, Richard A.
Jia, Wei
Sun, Qiang
Shi, Yufang
Wang, Ying
Candi, Eleonora
Melino, Gerry
author_facet Butera, Alessio
Agostini, Massimiliano
Cassandri, Matteo
De Nicola, Francesca
Fanciulli, Maurizio
D’Ambrosio, Lorenzo
Falasca, Laura
Nardacci, Roberta
Wang, Lu
Piacentini, Mauro
Knight, Richard A.
Jia, Wei
Sun, Qiang
Shi, Yufang
Wang, Ying
Candi, Eleonora
Melino, Gerry
author_sort Butera, Alessio
collection PubMed
description An essential function of the epidermis is to provide a physical barrier that prevents the loss of water. Essential mediators of this barrier function include ceramides, cholesterol, and very long chain fatty acids, and their alteration causes human pathologies, including psoriasis and atopic dermatitis. A frameshift mutation in the human ZNF750 gene, which encodes a zinc finger transcription factor, has been shown to cause a seborrhea-like dermatitis. Here, we show that genetic deletion of the mouse homolog ZFP750 results in loss of epidermal barrier function, which is associated with a substantial reduction of ceramides, nonpolar lipids. The alteration of epidermal lipid homeostasis is directly linked to the transcriptional activity of ZFP750. ZFP750 directly and/or indirectly regulates the expression of crucial enzymes primarily involved in the biosynthesis of ceramides. Overall, our study identifies the transcription factor ZFP750 as a master regulator epidermal homeostasis through lipid biosynthesis and thus contributing to our understanding of the pathogenesis of several human skin diseases.
format Online
Article
Text
id pubmed-10146900
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher American Association for the Advancement of Science
record_format MEDLINE/PubMed
spelling pubmed-101469002023-04-29 ZFP750 affects the cutaneous barrier through regulating lipid metabolism Butera, Alessio Agostini, Massimiliano Cassandri, Matteo De Nicola, Francesca Fanciulli, Maurizio D’Ambrosio, Lorenzo Falasca, Laura Nardacci, Roberta Wang, Lu Piacentini, Mauro Knight, Richard A. Jia, Wei Sun, Qiang Shi, Yufang Wang, Ying Candi, Eleonora Melino, Gerry Sci Adv Biomedicine and Life Sciences An essential function of the epidermis is to provide a physical barrier that prevents the loss of water. Essential mediators of this barrier function include ceramides, cholesterol, and very long chain fatty acids, and their alteration causes human pathologies, including psoriasis and atopic dermatitis. A frameshift mutation in the human ZNF750 gene, which encodes a zinc finger transcription factor, has been shown to cause a seborrhea-like dermatitis. Here, we show that genetic deletion of the mouse homolog ZFP750 results in loss of epidermal barrier function, which is associated with a substantial reduction of ceramides, nonpolar lipids. The alteration of epidermal lipid homeostasis is directly linked to the transcriptional activity of ZFP750. ZFP750 directly and/or indirectly regulates the expression of crucial enzymes primarily involved in the biosynthesis of ceramides. Overall, our study identifies the transcription factor ZFP750 as a master regulator epidermal homeostasis through lipid biosynthesis and thus contributing to our understanding of the pathogenesis of several human skin diseases. American Association for the Advancement of Science 2023-04-28 /pmc/articles/PMC10146900/ /pubmed/37115925 http://dx.doi.org/10.1126/sciadv.adg5423 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Biomedicine and Life Sciences
Butera, Alessio
Agostini, Massimiliano
Cassandri, Matteo
De Nicola, Francesca
Fanciulli, Maurizio
D’Ambrosio, Lorenzo
Falasca, Laura
Nardacci, Roberta
Wang, Lu
Piacentini, Mauro
Knight, Richard A.
Jia, Wei
Sun, Qiang
Shi, Yufang
Wang, Ying
Candi, Eleonora
Melino, Gerry
ZFP750 affects the cutaneous barrier through regulating lipid metabolism
title ZFP750 affects the cutaneous barrier through regulating lipid metabolism
title_full ZFP750 affects the cutaneous barrier through regulating lipid metabolism
title_fullStr ZFP750 affects the cutaneous barrier through regulating lipid metabolism
title_full_unstemmed ZFP750 affects the cutaneous barrier through regulating lipid metabolism
title_short ZFP750 affects the cutaneous barrier through regulating lipid metabolism
title_sort zfp750 affects the cutaneous barrier through regulating lipid metabolism
topic Biomedicine and Life Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10146900/
https://www.ncbi.nlm.nih.gov/pubmed/37115925
http://dx.doi.org/10.1126/sciadv.adg5423
work_keys_str_mv AT buteraalessio zfp750affectsthecutaneousbarrierthroughregulatinglipidmetabolism
AT agostinimassimiliano zfp750affectsthecutaneousbarrierthroughregulatinglipidmetabolism
AT cassandrimatteo zfp750affectsthecutaneousbarrierthroughregulatinglipidmetabolism
AT denicolafrancesca zfp750affectsthecutaneousbarrierthroughregulatinglipidmetabolism
AT fanciullimaurizio zfp750affectsthecutaneousbarrierthroughregulatinglipidmetabolism
AT dambrosiolorenzo zfp750affectsthecutaneousbarrierthroughregulatinglipidmetabolism
AT falascalaura zfp750affectsthecutaneousbarrierthroughregulatinglipidmetabolism
AT nardacciroberta zfp750affectsthecutaneousbarrierthroughregulatinglipidmetabolism
AT wanglu zfp750affectsthecutaneousbarrierthroughregulatinglipidmetabolism
AT piacentinimauro zfp750affectsthecutaneousbarrierthroughregulatinglipidmetabolism
AT knightricharda zfp750affectsthecutaneousbarrierthroughregulatinglipidmetabolism
AT jiawei zfp750affectsthecutaneousbarrierthroughregulatinglipidmetabolism
AT sunqiang zfp750affectsthecutaneousbarrierthroughregulatinglipidmetabolism
AT shiyufang zfp750affectsthecutaneousbarrierthroughregulatinglipidmetabolism
AT wangying zfp750affectsthecutaneousbarrierthroughregulatinglipidmetabolism
AT candieleonora zfp750affectsthecutaneousbarrierthroughregulatinglipidmetabolism
AT melinogerry zfp750affectsthecutaneousbarrierthroughregulatinglipidmetabolism