ZFP750 Affects the Cutaneous Barrier Through Regulating Lipid Metabolism

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2023 Apr 28

PMID 37115925

Authors

Alessio Butera

Massimiliano Agostini

Matteo Cassandri

Francesca De Nicola

Maurizio Fanciulli

Lorenzo DAmbrosio

Laura Falasca

Roberta Nardacci

Lu Wang

Mauro Piacentini

Richard A Knight

Wei Jia

Qiang Sun

Yufang Shi

Ying Wang

Eleonora Candi

Gerry Melino

Affiliations

Soon will be listed here.

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 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.

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