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 al-teration 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.

Butera, A., Agostini, M., Cassandri, M., De Nicola, F., Fanciulli, M., D’Ambrosio, L., et al. (2023). ZFP750 affects the cutaneous barrier through regulating lipid metabolism. SCIENCE ADVANCES, 9(17) [10.1126/sciadv.adg5423].

ZFP750 affects the cutaneous barrier through regulating lipid metabolism

Alessio Butera;Massimiliano Agostini
Membro del Collaboration Group
;
Matteo Cassandri;Laura Falasca;Mauro Piacentini;Eleonora Candi;
2023-01-01

Abstract

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 al-teration 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.
2023
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/11
English
Butera, A., Agostini, M., Cassandri, M., De Nicola, F., Fanciulli, M., D’Ambrosio, L., et al. (2023). ZFP750 affects the cutaneous barrier through regulating lipid metabolism. SCIENCE ADVANCES, 9(17) [10.1126/sciadv.adg5423].
Butera, A; Agostini, M; Cassandri, M; De Nicola, F; Fanciulli, M; D’Ambrosio, L; Falasca, L; Nardacci, R; Wang, L; Piacentini, M; Knight, Ra; Jia, W; ...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/358100
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