ZFP750 affects the cutaneous barrier through regulating lipid metabolism

Alessio Butera, Massimiliano Agostini, Matteo Cassandri, Francesca De Nicola, Maurizio Fanciulli, Lorenzo D’Ambrosio, Laura Falasca, Roberta Nardacci, Lu Wang, Mauro Piacentini, Richard A. Knight, Wei Jia, Qiang Sun, Yufang Shi, Ying Wang, Eleonora Candi, Gerry Melino*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

4 Citations (Scopus)

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 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.

Original languageEnglish
Article numbereadg5423
Number of pages17
JournalScience advances
Volume9
Issue number17
DOIs
Publication statusPublished - 28 Apr 2023

Scopus Subject Areas

  • General

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